Safety, immunogenicity, and effectiveness of the MAV/06 varicella vaccine: A comprehensive review of a new strain vaccine

ABSTRACT

Most of licensed varicella vaccines are based on the Oka strain, while MAV/06 strain vaccines were exclusively developed by GC Biopharma Corp. in South Korea. This paper aims to summarize and present more than 30 y of accumulated evidence from about 40 unpublished and published studies on safety, immunogenicity, and effectiveness of MAV/06 vaccines. The safety of MAV/06 vaccines has been confirmed through various clinical trials and post-marketing studies. Outstanding humoral and cell-mediated immunogenicity of the MAV/06 vaccines has been demonstrated in diverse clinical trials and real-world studies. For example, a seroconversion rate of the MAV/06 vaccine (BARYCELA inj.) was close to 100%. Moreover, several after-approval epidemiological studies in Korean and Filipino children have supported the effectiveness of MAV/06 vaccines, although it remains to be further confirmed in future studies. In terms of safety, immunogenicity, and effectiveness, MAV/06 strain varicella vaccines are comparable to Oka strain vaccines.

Introduction

Varicella-Zoster virus (VZV) is a type of herpesvirus with high infectivity, typically causing chickenpox in childhood and generally shingles in adulthood.^1–6 VZV belongs to the Herpesviridae family and is a double-stranded DNA virus, with only one serotype but divided into five major genotypes (clades 1 to 5). Clades 1 and 3 are usually found in Europe and America, clade 2 in Asia, clades 4, 5 in Africa.^4,5,7–9

The virus spreads through direct contact between individuals or inhalation of aerosol droplets from respiratory secretions of chickenpox patients, entering host cells via the upper respiratory tract or conjunctiva. After primary infection with VZV, the virus remains dormant in sensory ganglia and can later trigger shingles.^4–6,10

VZV is globally distributed, and in countries without national immunization programs (NIP), most individuals become infected by adolescence, with the highest incidence observed in preschool or early elementary school children. Chickenpox also exhibits a strong seasonal pattern in temperate and some tropical climates, with the highest incidence occurring between winter and spring. Outbreaks can occur periodically in schools or daycare centers.^{4–6,11–13} Globally, chickenpox affects over 140 million individuals annually, resulting in serious complications requiring hospitalization in over 4 million cases and causing over 4000 deaths.^5,6,14 Chickenpox significantly contributes to the burden of disease from secondary infections (e.g., group A streptococcal infections) among children.¹⁵ Most hospitalizations due to chickenpox occur in children, resulting in significant absenteeism from school and work for parents caring for sick children. Therefore, some countries have implemented vaccination programs during childhood to control chickenpox.⁵

The United States was the first country to introduce the one-dose varicella vaccine into its NIP program in 1995. Since then, several countries have been introducing the varicella vaccine as a universal vaccination program, with its effectiveness being demonstrated through various studies. In the United States, a two-dose program was introduced in 2006. After the introduction of the varicella vaccine in 1995, it became evident that one dose was insufficient to fully prevent chickenpox. Therefore, to further enhance immunity against chickenpox, maintain long-term immunity, reduce breakthrough infections, and prevent severe cases, the U.S. Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) recommended a 2-dose varicella vaccine schedule in 2006, which was subsequently integrated into the NIP. During 25 y after the introduction of the varicella NIP in the United States, the incidence of chickenpox has decreased by over 97% in all age groups, and particularly 99% in individuals under 20 y of age.^5,16–18 In most countries where the varicella vaccine has been introduced into national vaccination programs, incidence and hospitalization rates have decreased by over 80%, indicating that vaccination is an effective method for preventing chickenpox. Therefore, the introduction of a varicella NIP has been recommended from a public health and economic perspective.^5,14,19,20

However, there are still many countries that have not introduced the varicella vaccine as a NIP.^16,19–28 In particular, most low-income countries in Africa lack a varicella NIP.^16,19,29 And within low- and middle-income countries, generally, vaccination coverage is lower in the children with low socioeconomic background (household wealth and mother’s education level).³⁰ Cost-effective varicella vaccines are an essential prerequisite for increasing vaccine coverage and reducing vaccination inequality particularly among the children in low- and middle-income countries. The cost-effectiveness of a vaccine is a crucial decision-making point for governments, especially those of low- or middle-income countries, to introduce the varicella vaccine into their NIPs and expand vaccination coverage.

The currently licensed vaccines for preventing chickenpox are the live attenuated vaccines, which include the Oka strain and the MAV/06 strain. Although both strains belong to clade 2 and are genetically very similar,^31–34 the majority of varicella vaccines used worldwide are derived from the wild-type pOka (parental Oka, a wild-type clinical isolate of the VZV) virus. Oka strain varicella vaccines are produced by Biken, MSD, GSK, and other manufacturers in China, among others.^5,16,35,36 On the other hand, varicella vaccines derived from MAV/06 strain were exclusively developed by GC Biopharma Corp. in South Korea.^37,38 Among these, varicella vaccines from MSD, SK Bioscience, Sinovac, and GC Biopharma corp. are prequalified by the World Health Organization (WHO). These vaccines have met the criteria set by the WHO and are eligible for bidding at WHO and UN agencies³⁹ (Table 1).

Table 1.

Examples of marketed varicella vaccines.^{5,17,35,36,39}

Strain	Trade Name	Manufacturer	Country	WHO prequalification
Oka/Biken	OKAVAX	Biken	Japan	–
Oka/Merck	VARIVAX	MSD	USA	Yes
Oka/RIT	VARILRIX	GSK	Belgium	–
Oka	VARI-L	Changchun Keygen Biological Products	China	–
Oka	Varicella Vaccine, Live	Sinovac	China	Yes
Oka/SK	SKYVaricella	SK Bioscience	S.Korea	Yes
MAV/06	Varicella Vaccine-GCC inj. (Suduvax)	GC Biopharma Corp.	S.Korea	–
MAV/06	BARYCELA	GC Biopharma Corp.	S.Korea	Yes

Although more than 30 million doses of MAV/06 vaccines have been distributed internationally, there is no comprehensive review on safety, immunogenicity, and effectiveness of MAV/06 vaccines in the literature. In addition, despite some published papers,^{37,38,40–43} significant pieces of information on safety, immunogenicity, and effectiveness of MAV/06 vaccines have remained unpublished as internal documents of GC Biopharma Corp. As a result, the strengths and weaknesses of MAV/06 strain vaccines, a potential cost-effective alternative to Oka strain vaccines, have not been fully discussed and understood among global vaccine stakeholders.

The objective of this study is to provide a comprehensive review of the characteristics, safety, immunogenicity, and effectiveness of the MAV/06 varicella vaccine developed by GC Biopharma Corp., and qualified by the WHO for routine childhood immunization in many countries.

Methods

We conducted an extensive literature review of all peer-reviewed published articles during 1991–2023 about MAV/06 vaccines regarding safety, immunogenicity, and effectiveness. In addition, in our review, we included ten unpublished, but important and latest official documents of MAV/06 vaccines, issued by or submitted to regulatory authorities.

Characteristics of MAV/06 varicella vaccines

Development history

Isolation of MAV strain

According to research conducted by the Mogam Biotechnology Research Institute,^37,38 varicella viruses were isolated from vesicles of seven patients who presented with chickenpox symptoms at a pediatric clinic in Seoul, South Korea, in 1989 (Table 2).

Table 2.

Isolation of varicella-zoster virus from vesicle fluid of varicella patients.³⁸

Isolate	Clinical Symptom	Ages(months)/Sex
MAV1/1	Varicella	22/Male
MAV/2	Varicella	16/Male
MAV/3	Varicella	20/Male
MAV/4	Varicella	45/Female
MAV/5	Varicella	28/Female
MAV/6	Varicella	33/Male
MAV/7	Varicella	23/Male

¹MAV (MogAm Virus).

Attenuation of MAV/06 strain

To attenuate the obtained varicella viruses, several passages were carried out in normal human embryonic lung diploid cells (LuMa, normal human embryonic Lung diploid MogAm) and normal guinea pig lung diploid cells (GEL) through multiple cultivation steps (Table 3). To confirm the degree of attenuation, temperature sensitivity tests and cell susceptibility tests, which were previously used in the attenuation of the Oka virus strain⁴⁴ were employed. Among the varicella viruses tested, the sixth virus (designated MAV/06 virus) exhibited the highest cell susceptibility and the lowest temperature sensitivity. The lowest virus infectivity ratio at 39°C/34°C since it best adapts to the temperature condition of 34°C and GEL cells, and at the same time, has the highest virus infectivity ratio in GEL/LuMA cells. When the MAV/06 was subcultured, the temperature sensitivity shown from p45 to p60 was 0.05 to 0.07, and this was at a level similar to the temperature sensitivity result of 0.03 of the Oka vaccine strain. In addition, the cellular susceptibility of the MAV/06 virus strain from p45 to p60 was 0.80 to 0.83, and this could be confirmed via references to be at a level similar to the result of 0.82 of the Oka vaccine strain. Therefore, it was selected as the attenuated varicella virus strain for GC Biopharma Corp.’s varicella vaccine.³⁷

Table 3.

Number of passage levels in the MAV/06 strain for attenuation.³⁷

Cell	Passage Number	Remark
HEL1	11	LuMa2 cell
GEL3	13	–
HEL	8	LuMa cell
HEL	4	MRC-54 cell
HEL	24	LuMa cell

¹HEL (Human Embryonic Lung diploid cell), ²LuMa (normal human embryonic Lung diploid MogAm), ³GEL (Guinea-pig Embryonic Lung diploid cell), ⁴MRC-5 (Medical Research Council cell strain 5).

Subsequent sequencing studies of varicella vaccines revealed 42 known single nucleotide polymorphisms (SNPs) occurring during the attenuation process from wild type to attenuated varicella viruses.^31,33,45,46 In particular, open reading frame (ORF) 0 and ORF 62 of VZV genome have been reported to be associated with the vaccine attenuation.^33,35,47 Read-through mutation at stop codon in ORF 0 is one of the attenuation genotypes of vaccine VZVs, which might be an important feature distinguishing vaccine strains from pOka strains.⁴⁷ Also, during attenuation, genetic variants accumulated in ORF 62 which is essential for viral replication and spreading, are important in determining the level of attenuation of VZV vaccines.³³ To confirm whether the MAV/06 vaccine was well attenuated, sequencing comparison studies were conducted with Oka-derived varicella vaccines. The results showed that levels of nucleotide sequence variations at the 42 SNP positions were similar between the MAV/06 vaccine and vOka-derived varicella vaccines such as VARILRIX and VARIVAX. For example, the nucleotide sequences of MAV/06 were the same as those of VARILRIX at 38 out of 42 (90.5%) SNP positions and those of VARIVAX at 30 out of 42 (71.4%) SNP positions. In addition, MAV/06 shared the same nucleotide sequences with VARILRIX and VARIVAX at all of the three SNP positions (560, ORF0; 106262, ORF62; and 107252, ORF62) known to be strongly associated with the vaccine attenuation.³⁵ Based on these findings, it was confirmed that the MAV/06 vaccine was well attenuated.^31,47

Genomic characteristics of MAV/06 strain

• Genotyping

  To date, there are multiple VZV strains whose whole genome sequence has been identified, and their nature can be divided into the pathogenic wild-type (Dumas and pOka, Table 4), which induces disease in humans, and the vaccine-type, which induces defensive immunity. The Oka strain (vOka, VARILRIX, and VARIVAX) and the MAV/06 strain (BARYCELA inj. and Varicella Vaccine-GCC inj. (Suduvax), Table 4).

  As a result, the whole genome sequence length of the MAV/06 strain was 124,758 bp, and the structure of VZV consisting of TR_L, U_L, IR_L, IR_S, U_S, and TR_S was identified. This confirms that the MAV/06 virus does not exhibit significant differences compared to other representative wild-type viruses and vOka-derived viruses³⁴ (Table 4).

• Clade analysis

  The MAV/06 vaccine underwent whole-genome sequencing in three studies, allowing for the confirmation of its genetic characteristics. The results of the whole-genome sequencing revealed that the MAV/06 vaccine belongs genetically to the same clade (Clade 2) as the well-known Oka-derived vaccines (VARIVAX, VARILRIX, and Biken)^31,34,47 (Figure 1).

Table 4.

Genome structure of VZV strain.³⁴

Strain	Accession Number	Full Length (bp)	Length (bp)
			TRL1	UL2	IRL3	IRS4	US5	TRS6
Dumas	NC001348	124,884	88	104,836	88	7,320	5,232	7,320
pOka*	AB097933	125,125	88	104,798	88	7,463	5,225	7,463
vOka*	AB097932	125,078	88	104,822	88	7,427	5,232	7,421
VARILRIX	DQ008354	124,821	88	104,761	88	7,326	5,231	7,327
VARIVAX	DQ008355	124,815	88	104,758	88	7,324	5,232	7,325
MAV/06*	JF306641	124,758	88	104,798	88	7,276	5,232	7,276

¹TR_L (Terminal long repeat); ²U_L (Unique long region); ³IR_L (Internal long repeat); ⁴IR_S (Internal short repeat); ⁵U_S (Unique short region); ⁶TR_S (Terminal short repeat); *pOka (parental Oka), *vOka (vaccine Oka), *MAV/06 (BARYCELA inj. & Varicella Vaccine-GCC inj).

Figure 1.

Phylogentic tree showing five major varicella zoster virus (VZV) clades include Oka & MAV/06.^31,34,47.

Product information on MAV/06 strain vaccines

There are two varicella vaccines that are derived from the MAV/06 strain: BARYCELA inj. and Varicella Vaccine-GCC inj. (Suduvax).

Varicella Vaccine-GCC inj. was developed by GC Biopharma Corp. using MAV/06 strain and LuMA cell line, which became the world’s second licensed varicella vaccine in 1993.^34,47,48

The second generations MAV/06 varicella vaccine, BARYCELA inj., was developed by GC Biopharma Corp. using MAV/06 strain and MRC-5 cell line and licensed in 2020.⁴⁹ BARYCELA inj. features an enhanced manufacturing process and greater stability compared to Varicella Vaccine-GCC inj. Antibiotic additives are generally used to prevent contamination of cells during a manufacturing process of vaccines. There are possibilities that these antibiotics may cause ADRs such as anaphylaxis in some people after administration.⁵⁰ BARYCELA inj. is the world’s first and only antibiotic-free varicella vaccine that eliminates the risk of adverse reactions and assures improved safety.^51–55

• Varicella Vaccine-GCC inj. (Suduvax)^48,56,57

  For each vial of Varicella Vaccine-GCC inj., not less than 1400 PFU of live attenuated VZVs are supplied in lyophilized powder. In addition to the active ingredient, each vial contains the following ingredients: Sucrose (as a stabilizer), Glycine (as a stabilizer), Sodium L-glutamate hydrate (as a stabilizer), Gelatin (as a stabilizer), L-cysteine (as a stabilizer), Edetate disodium (as a stabilizer); Na₂HPO₄.12 H₂O (as a buffer) and NaH₂PO₄.2 H₂O (as a buffer). For each annexed vial of diluent, a volume of 0.7 mL sterile water for injection is included in a kit. Varicella Vaccine-GCC inj. becomes a transparent colorless or yellowish solution when reconstituted with the diluent supplied and is stored at 2–8°C with a shelf life of 2 y. For the use in children and adults, this vaccine is subcutaneously injected into the outer aspect of the upper arm (deltoid region).

• BARYCELA inj.^49,51

  For each vial of BARYCELA inj., not less than 3800 PFU of live attenuated VZVs are supplied in lyophilized powder. In addition to the active ingredient, each vial contains the following ingredients: Sucrose (as a stabilizer), Glycine (as a stabilizer), Sodium L-glutamate hydrate (as a stabilizer), Gelatin (as a stabilizer), L-cysteine (as a stabilizer), Disodium edetate hydrate (as a stabilizer), Urea (as a stabilizer); Dibasic sodium phosphate hydrate (as a buffer), Potassium dihydrogen phosphate (as a buffer). For each enclosed vial of diluent, a volume of 0.7 mL sterile water for injection is included in a kit. BARYCELA inj. becomes a transparent colorless or pale-yellow solution when reconstituted with the diluent supplied and is stored at 2–8°C with a shelf life of 2 y. For the use in children, this vaccine is subcutaneously injected into the outer aspect of the upper arm (deltoid region).

Registration and distribution

Registration

• Varicella vaccine-GCC inj. (Suduvax)⁴⁸

  Varicella Vaccine-GCC inj. was first approved in 1993 in South Korea and later approved in other Asian and South American countries (Table 5).

• BARYCELA inj.^{49,51,58–60}

  BARYCELA inj. was first approved in 2020 and launched in 2021 in South Korea. It was included in the list of prequalified varicella vaccines by the World Health Organization (WHO) in 2023 (Table 5). In the same year, this vaccine was approved in Pakistan. In 2024 and 2025, it was also approved in Turkiye and Vietnam. As of 2025, regulatory approval processes are underway in about eight countries, including Saudi Arabia in Asia, and countries in South America such as Brazil and Argentina.

Table 5.

Worldwide market authorization status (as of July 2025).^{48,49,51,58–60}

Vaccine	Country	Approved date	Trade Name
Varicella Vaccine-GCC inj.	S.Korea	June, 1993	Suduvax inj.
	Peru	March, 2000	Varicella vaccine KGCC
	Dominica	December, 2000	VACUNA DE VARICELA GCC, 1400 PFU/0.7 mL
	Indonesia	September, 2001	Varicella vaccine KGCC
	Philippines	June, 2005	V-z vax
	Egypt	August, 2006	Varicella vaccine GCC
	Thailand	March, 2007	Varicella vaccine-GCC inj.
	Vietnam	October, 2008	Varicella vaccine-GCC inj.
	Colombia	September, 2011	Vacuna contra la varicella GCC inyeccion
	Guatemala	April, 2019	Vacuna contra la Varicela
BARYCELA inj.	S.Korea	March, 2020	BARYCELA inj.
	WHO	February, 2023	BARYCELA inj.
	Pakistan	June, 2023	BARYCELA inj.
	Turkiye	September, 2024	BARYCELA inj.
	Vietnam	July, 2025	BARYCELA inj.

Distribution

• Varicella Vaccine-GCC inj. (Suduvax)⁴⁸

  Varicella Vaccine-GCC inj. has been shipped and exported to 26 countries, totaling over 29 million doses (Total 26 countries; Aruba, Anguilla, Antigua and Barbuda, Barbados, Bahamas, Bermuda, Brazil, British Virgin Islands, Cayman Islands, Chile, Colombia, Costa Rica, Ecuador, Grenada, Guatemala, Nepal, Panama, Paraguay, Philippines, S.Korea, Saint Lucia, Saudi Arabia, Thailand, Trinidad and Tobago, Turkiye, Vietnam).

• BARYCELA inj.⁶¹

  BARYCELA inj. has been shipped and exported to six countries, totaling over 520,000 doses (Total six countries; Aruba, Antigua and Barbuda, Guatemala, S.Korea, Saint Lucia, Trinidad and Tobago).

• Over the past 30 y, MAV/06 varicella vaccines have been distributed to over 20 countries worldwide, totaling approximately 30 million doses. Through the Pan American Health Organization (PAHO) bidding, the vaccines have been stably supplied to countries in Central and South America. Throughout this process, MAV/06 varicella vaccines have been confirmed as the most cost-effective option, offering the most rational pricing in terms of cost^62–64 (Table 6). On average, the price of the MAV/06 vaccine supplied to the PAHO was 20% lower than that of the Oka vaccines during 2021–2023 according to the PAHO.

Table 6.

Varicella vaccine prices disclosed on PAHO (US$ per dose).^62–64

Strain	2021	2022	2023	Average
Oka	16.93	16.19	16.93	16.68
MAV/06	13.80	12.50	12.50	12.93

Clinical studies of MAV/06 varicella vaccines

Safety, immunogenicity, and effectiveness

Safety

The evidence of the safety of MAV/06 vaccines has been accumulated and demonstrated through several clinical trials and 30 y of real-world use. The secured safety data is as follows:

• Evidence from clinical trials

  The safety of the MAV/06 vaccine has been confirmed through various clinical trials. When summarizing the safety results obtained from these trials, the following points emerge:

  MAV/06 vaccine has demonstrated satisfactory safety profiles across different age groups, including infants, children, adolescents, and adults.

  Safety assessments conducted in both healthy individuals and those with compromised immune function (such as immunocompromised infants) have shown satisfactory outcomes.

  No significant differences in safety profiles were observed between MAV/06 vaccine and comparator vaccine (such as VARIVAX) in randomized controlled trials.

  The vaccine exhibited satisfactory safety outcomes at different dosage levels, ranging from 300 PFU to 25,000 PFU.

  Safety assessments conducted in various countries, including S.Korea, Thailand, the Philippines, and Vietnam, have consistently confirmed the safety of MAV/06 vaccine across diverse populations.

  Overall, the comprehensive safety data obtained from multiple clinical trials support the conclusion that the MAV/06 vaccine is safe for use in the prevention of varicella infection (Table 7).

  More detailed information on safety is presented in a chronological order: the first three clinical trial studies were about the safety of Varicella Vaccine-GCC inj. They were followed by the three clinical trial studies (Phases I, II, and III, respectively) on the safety of BARYCELA inj. The last study, a clinical trial for registration of BARYCELA inj. in Vietnam, provided additional safety information.

1. Safety and immunogenicity of live attenuated varicella vaccine (MAV/06 strain) in adults and children (1994).⁴⁰

   In Korea, safety was confirmed by administering MAV/06 vaccines ranging from 300 PFU to 2,000 PFU to a total of 62 healthy adults and children (30 adults, 32 infants).

   After vaccination, changes and local symptoms such as pain, swelling, redness, induration, and tenderness at the injection site were observed for 72 hours. The occurrence of systemic reactions such as fever, headache, nausea, vomiting, skin rash, and vesicular rash was observed for 4 weeks. In this regard, safety issues were not observed, and no serious adverse events were reported.

2. Immunogenicity and safety of live attenuated vaccine (MAV/06 strain) on healthy children and immunocompromised children (1995).⁴¹

   In Korea, safety was confirmed by administering the MAV/06 vaccine to a total of 177 healthy infants, children, and adolescents (aged 12 months to 19 y), as well as 22 immunocompromised infants (who had undergone medical treatment for conditions such as 6 leukemia, 10 solid tumors, and 6 nephrotic syndromes, but were in clinical remission and had a minimum level of immunocompetence: peripheral lymphocyte count ≥700/mm³ and serum IgG level ≥100 mg/dL). No unusual adverse events were observed.

3. Immunogenicity and safety of a new live attenuated varicella vaccine (MAV/06 strain) among healthy Filipino children of ages 9 months to 17 y (2001).⁶⁵

   In the Philippines, the MAV/06 vaccine was administered to a total of 375 healthy infants and children (aged 9 months to 17 y). Safety was assessed by dividing the participants into age-specific groups, and the vaccine was well tolerated with no serious or unusual adverse events were reported.

4. A single-center, dose block-randomized, single-blind, active-controlled, dose-escalation phase I clinical trial to evaluate the safety and efficacy of MG1111 (BARYCELA inj.) in healthy adults (2015).^66,67

   In Korea, a total of 39 healthy adults were recruited, with the WHO pre-qualified vaccine VARIVAX serving as the control vaccine. The BARYCELA inj. vaccine was administered at different doses (2,000 PFU, 8,000 PFU, 25,000 PFU) to assess safety.

   The safety evaluation was based on solicited adverse events that occurred within 7 d after the administration of the BARYCELA inj., unsolicited adverse events that occurred within 42 d after the administration of the BARYCELA inj., and the results of laboratory tests, vital signs, and physical examination. The occurrence rates of overall adverse events that occurred during the clinical study period by treatment group were 80.00% (8 of 10 subjects; 26 cases) in the 2,000 PFU group, 40.00% (4 of 10 subjects; 13 cases) in the 8,000 PFU group, 60.00% (6 of 10 subjects; 18 cases) in the 25,000 PFU group, and 55.56% (5 of 9 subjects; 19 cases) in the VARIVAX group. The occurrence rates of overall ADRs by treatment group were 60.00% (6 of 10 subjects; 20 cases) in the 2,000 PFU group, 40.00% (4 of 10 subjects; 11 cases) in the 8,000 PFU group, 60.00% (6 of 10 subjects; 14 cases) in the 25,000 PFU group, and 55.56% (5 of 9 subjects; 15 cases) in the VARIVAX group, which were similar to each other. No serious adverse events occurred during the clinical study period (ClinicalTrials.gov ID; NCT02367638).

5. A Phase II, single-blind, randomized, multi-center, active-controlled, dose-escalation study to evaluate safety and efficacy of MG1111 (BARYCELA inj.) in healthy children (2017).^68,69

   In Thailand, a total of 299 healthy infants and children (aged 12 months to 12 y) were recruited. The WHO pre-qualified vaccine VARIVAX served as the control vaccine. The BARYCELA inj. vaccine was administered at different doses (2,000 PFU, 8,000 PFU, 25,000 PFU) to assess safety. A total of 212 (70.9%) subjects reported 969 Adverse Events with most Adverse Events (283 events in 63 subjects [82.9%]) in 25,000 PFU, followed by VARIVAX (249 events in 51 subjects [69.9%]), 2,000 PFU (238 events in 50 subjects [66.7%]), and 8,000 PFU (199 events in 48 subjects [64.0%]). The p-value based on Chi-square/Fisher’s exact test indicated that there was no statistically significant difference in the number of subjects with adverse events between the BARYCELA inj. groups (2,000 PFU, 8,000 PFU, and 25,000 PFU) and VARIVAX. Vaccination with all groups was safe and well-tolerated in subjects aged 12 months to 12 y (ClinicalTrials.gov ID; NCT03375502).

6. Immunogenicity and safety profiles of MG1111 (BARYCELA inj.) in healthy children: A multinational, multicenter, randomized, double-blinded, active-controlled phase III study (2018).^42,68,69

   In both Korea and Thailand, a total of 515 healthy infants and children (aged 12 months to 12 y) were recruited. The WHO pre-qualified vaccine VARIVAX served as the control vaccine. The subjects were randomly assigned in a 1:1 ratio, with 258 subjects receiving BARYCELA and 257 subjects receiving VARIVAX. A total of 394 subjects (76.5%) reported 2180 Adverse Events: BARYCELA inj. (1,109 events in 202 subjects [78.3%]) and VARIVAX (1,071 events in 192 subjects [74.7%]). The p-value based on Chi-square/Fisher’s exact test indicated that there was no statistically significant difference in the number of subjects with Adverse Events between the BARYCELA inj. groups and VARIVAX. It was confirmed that there were no significant differences compared to the control group (ClinicalTrials.gov ID; NCT03375502).

7. An open-label, bridging study to assess the safety and immunogenicity of BARYCELA inj. in healthy Vietnamese children aged between 12 months and 12 y (2024).^70,71

   In Vietnam, a total of 250 healthy infants and children were vaccinated with BARYCELA vaccine. Safety was assessed by dividing the participants into age-specific groups, and safety findings continue to support good safety profile in healthy children aged 12 months to 12 y. Satisfactory safety was confirmed in all groups (ClinicalTrials.gov ID; NCT05664152).

• Evidence from post-marketing real world uses

  Once a medicine receives regulatory approval and is marketed, periodic benefit-risk evaluation reports (PBRER), previously known as Periodic Safety Update Reports (PSUR), are prepared according to the ICH E2C (R2) guideline.⁷²

  As of March 2024, four reports have been compiled for Varicella Vaccine-GCC inj., while six reports have been prepared for BARYCELA inj. These reports include information on the quantities of vaccines supplied during a specific period and adverse reaction cases reported in the field during that period.

  Varicella Vaccine-GCC inj. was distributed a total of 29,224,770 doses from 2005 to June 2022. Among these, there were 120 reports about ADRs. BARYCELA inj. has been distributed 528,360 doses since 2020 and 3 voluntary adverse reaction reports have been accumulated^48,61 (Table 8).

  Although direct comparison may be limited due to differences in pharmacovigilance reporting systems among manufacturers and countries, as well as variations in reporting practices across nations, incidence rates of reported adverse events are lower for MAV/06 vaccines than for other varicella vaccines in post-approval settings (Table 9).^73–75

• Strain interchangeability

  Some countries have incorporated a two-dose regimen of varicella vaccine into their NIP, and the WHO also recommends a two-dose vaccination to further reduce the incidence of varicella cases and to decrease outbreaks in the community.⁶

  In line with this, a study was conducted to assess the safety of cross-vaccination with MAV/06 and vOka-derived vaccines when administered in a two-dose regimen.⁴³

  The study involved a total of 406 Korean infants, who received the first and second doses of vaccination with MAV/06-vOka, vOka-MAV/06, MAV/06-MAV/06 and vOka-vOka, respectively. The study confirmed that there were no safety concerns associated with this cross-strain vaccination regimen. The recent WHO position paper stated that “Interchanging the Oka and MAV/06 strain live attenuated varicella vaccines showed no safety signals in one small trial including healthy children.”⁶

• Antibiotic-free

  Antibiotics (e.g., Kanamycin, Neomycin, and Erythromycin) are generally used to prevent contamination of cells during a manufacturing process of vaccines. There are possibilities that these antibiotics may cause ADRs such as anaphylaxis in some people after administration.⁵⁰ However, BARYCELA inj. is a varicella vaccine that does not contain antibiotics, thus eliminating the risk of adverse reactions associated with antibiotics.^51,53–55

Table 7.

Safety information of MAV/06 vaccines confirmed through clinical trials.

Clinical trial (year)	Cohort	Number of subjects by cohort	Country
1994*40	300 PFU1 500 PFU 1,000 PFU 1,500 PFU 2,000 PFU	6 children 7 children 19 adults, 13 children 6 children 11 adults	S.Korea
1995*41	Healthy children Immunocompromised children	177 children 22 children (6 leukemia, 10 solid tumors, 6 nephrotic syndromes)	S.Korea
2001*65	9–12 months 1–12 y 13–17 y	102 children 172 children 101 children	Philippines
2015**66,67	2,000 PFU 8,000 PFU 25,000 PFU	10 adults 10 adults 10 adults	S.Korea
2017**68,69	2,000 PFU 8,000 PFU 25,000 PFU	75 children 75 children 76 children	Thailand
2018**42,68,69	MG11112	258 children	S.Korea/Thailand
2024**70,71	12–24 months 2–12 y	124 children 126 children	Vietnam

¹PFU: Plaque Forming Unit, ²MG1111: project code of BARYCELA, *Varicella Vaccine-GCC inj., **BARYCELA inj.

Table 8.

Summary of PBRER (PSUR) for Varicella Vaccine-GCC inj. and BARYCELA inj.^48,61

Vaccine	Report version	Reporting Period	Distribution (vials)	Overall reported ADRs1 cases	Conclusion
Varicella Vaccine-GCC inj.	PSUR v1.0	January 2005–June 2013	6,512,915	3	There were no new safety issues associated with Varicella Vaccine-GCC inj. during this PSUR reporting period
	PSUR v2.1	June 2013–June 2016	5,070,608	30	There were no new safety issues associated with Varicella Vaccine-GCC inj. during this PSUR reporting period
	PBRER v3.0	June 2016–June 2019	11,475,897	77	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	PBRER v4.0	June 2019–June 2022	6,165,350	10	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	Total		29,224,770	120	–
BARYCELA inj.	PBRER v1.0	March 2020–September 2020	– *	–	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	PBRER v2.0	September 2020–March 2021	– *	–	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	PBRER v3.0	March 2021–September 2021	– *	–	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	PBRER v4.0	September 2021–March 2022	52,070	–	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	PBRER v5.0	March 2022–March 2023	182,980	1	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	PBRER v6.0	March 2023–March 2024	293,310	2	No new relevant safety findings which would necessitate an analysis and a change in the current reference safety information
	Total		528,360	3	–

¹ADRs: Adverse Drug Reactions, *No launch.

Table 9.

Comparison of the incidence of reported adverse events between MAV/06 and Oka vaccines during post-approval use periods.^{48,61,73–75}

Strain	Oka			MAV/06
Vaccine	VARIVAX1	VARIVAX2	OKAVAX3	Varicella Vaccine-GCC inj.	BARYCELA inj.
Total number of vials distributed	16,100,000	55,700,000	9,467,000	29,224,770	528,360
Number of reported adverse events	7,963	16,683	351	120	3
Estimated incidence rates (/100,000 doses)	49.46	29.95	3.71	0.41	0.57

¹R.G. Sharrar et al.^{75 2}S.A. Galea et al.^{74 3}Yosikawa et al.⁷³.

Immunogenicity

The gold standard test for measuring VZV antibodies is the Fluorescent Antibody to Membrane Antigen (FAMA) assay, developed in the 1970s. Additionally, the glycoprotein enzyme-linked immunosorbent assay (gpELISA) is commonly used. Generally, an FAMA antibody titer of 1:4 or higher is considered seropositive, indicating protection against varicella.^5,76,77

The immunogenicity of MAV/06 vaccines have been investigated tested through several clinical trials and studies.

• Results of clinical trials

  Through various clinical trials, high post-vaccination antibody titers and very high seroconversion rates (SCRs) have been confirmed. Seroconversion was defined as an increase in antibody titer of 1:4 or higher from seronegative status by FAMA assay at 42 d after administration of the vaccines.

  In South Korea, the SCR of MAV/06 vaccines (BARYCELA inj. and Varicella Vaccine-GCC inj.) were close to 100% in healthy infants and children aged 12 months to 19 y, and immunocompromised children.

  In the Philippines, healthy infants and children aged 9 months to 17 y, the SCR of Varicella Vaccine-GCC inj. was close to 100% at both 6 weeks and 5 y after vaccination.

  In Thailand, the SCR of BARYCELA inj. was close to 100% in healthy infants and children aged 12 months to 12 y.

  In Vietnam, healthy infants and children, high antibody titers of 69.9 and 126.5 were observed after vaccination with BARYCELA inj. (Table 10).

1. Safety and immunogenicity of live attenuated varicella vaccine (MAV/06 strain) in children⁴⁰

   In South Korea, a total of 32 healthy children with negative FAMA antibodies before vaccination were vaccinated with MAV/06 vaccine doses ranging from 300 PFU to 1000 PFU to confirm immunogenicity. The results showed that regardless of the vaccine dose, children had a 100% SCR and high antibody levels 4 weeks after vaccination.

2. Immunogenicity and safety of live attenuated vaccine (MAV/06 strain) on healthy children and immunocompromised children⁴¹

   In South Korea, a total of 161 healthy children and adolescents (aged 12 months to 19 y) and 18 immunocompromised children (who had undergone medical treatment for conditions such as 6 leukemia, 10 solid tumors, and 6 nephrotic syndromes, but were in clinical remission and had a minimum level of immunocompetence: peripheral lymphocyte count ≥700/mm³ and serum IgG level ≥ 100 mg/dL) were vaccinated with MAV/06 vaccine to confirm immunogenicity. After 4 weeks, both healthy children and immunocompromised children showed a 100% SCR.

3. Immunogenicity and safety of a new live attenuated varicella vaccine (MAV/06 strain) among healthy Filipino children of ages 9 months to 17 y.⁶⁵

   In the Philippines, a total of 299 healthy infants and children (aged 9 months to 17 y) were vaccinated with MAV/06 vaccine, and immunogenicity was assessed by age group. The overall SCR was confirmed to be 99.7% six weeks after vaccination.

4. A 5-y follow-up immunogenicity of a new live attenuated varicella vaccine (MAV/06 strain) among healthy Filipino children of ages 9 months to 17 y.⁷⁸

   In 2001, a clinical study was conducted in the Philippines to assess the immunogenicity and safety of the vaccine.⁶⁵ Five years later, long-term immunogenicity and protective efficacy were evaluated. Among the 299 healthy children enrolled in the study, 163 were followed up, and 162 of them were confirmed to be seropositive (99.4%). Values greater than 4.0 FAMA antibody titer are regarded as seropositive for varicella zoster IgG antibody.

5. A single-center, dose block-randomized, single-blind, active-controlled, dose-escalation phase I clinical trial to evaluate the safety and efficacy of MG1111 (BARYCELA inj.) in healthy adults.^66,67

   In a study conducted in Korea, a total of 39 healthy adults were vaccinated with BARYCELA inj. at different doses (2,000 PFU, 8,000 PFU, 25,000 PFU) with WHO pre-qualified vaccine VARIVAX as the control vaccine. After 6 weeks, the FAMA geometric mean titer (GMT) results for each dose were found to be 78.8, 90.5, and 68.6, respectively (ClinicalTrials.gov ID; NCT02367638).

6. A Phase II, single-blind, randomized, multi-center, active-controlled, dose-escalation study to evaluate immunogenicity and safety of MG1111 (BARYCELA inj.) in healthy children.^68,69

   In a study conducted in Thailand, a total of 193 healthy infants and children (12 months to 12 y) were vaccinated with BARYCELA inj. at different doses (2,000 PFU, 8000 PFU, 25,000 PFU) with WHO pre-qualified vaccine VARIVAX as the control vaccine. After 6 weeks, the results showed a 100% SCR for each dose, with GMT results of 85.5, 109.9, and 65.6, respectively (ClinicalTrials.gov ID; NCT03375502). The criteria for seroconversion was met in 43 of the 43 subjects (100%, 95% confidence interval [CI]: 91.78, 100) in the 2,000 PFU, 41 of the 41 subjects (100%, 95% CI: 91.40, 100) in the 8000 PFU, 57 of the 57 subjects (100%, 95% CI: 93.73, 100) in the 25,000 PFU, and 52 of the 52 subjects (100%, 95% CI: 93.15, 100) in VARIVAX.

7. Immunogenicity and safety profiles of MG1111 (BARYCELA inj.) in healthy children: A multinational, multicenter, randomized, double-blinded, active-controlled phase III study.^42,68,69

   In both Korea and Thailand, a total of 478 healthy infants and children (aged 12 months to 12 y) were enrolled in a randomized, 1:1 controlled trial, with WHO pre-qualified vaccine VARIVAX as the control vaccine and BARYCELA as the test vaccine (239 subjects in each group). After 6 weeks, the test group showed non-inferiority compared to the control group in terms of immunogenicity. The results of SCR as the primary immunogenicity measure were 97.9% and 99.2% for the test and control groups, respectively. The lower limit of 95% CI for SCR difference (MG1111-VARIVAX) was −4.0%, which was higher than the pre-specified non-inferiority margin of −10%. The results of GMT as a secondary immunogenicity measure were 74.2 and 112.7, respectively (ClinicalTrials.gov ID; NCT03375502).

8. An open-label, bridging study to assess the safety and immunogenicity of MG1111 (BARYCELA inj.) in healthy Vietnamese children aged between 12 months to 12 y.^70,71

   In Vietnam, a total of 246 healthy infants and children were vaccinated with the BARYCELA vaccine. They were divided into age-specific groups to assess immunogenicity. After 6 weeks, the GMT results for each age group were 69.9 and 126.5, respectively (ClinicalTrials.gov ID; NCT05664152).

• Results of seroprevalence study

  In 2016, a study conducted in South Korea examined the seropositivity rate among total 715 children who received the varicella vaccines distributed in Korea. In the study, the seropositivity of the MAV/06 vaccine using the FAMA test was 74%, while the seropositivity of a vOka derived vaccine (Vari-L) was 63%.⁷⁹ This result is similar to the findings from previous studies conducted in the United States in 2006 (76%)^5,80 and in Korea in 2010 (83.6%)⁷⁶ (Table 11).

  Furthermore, in a Korean study,⁷⁹ there was a tendency that antibody levels (assessed with gpELISA tests) decreased as age of children increased from 1 to 4 y. However, there was no significant difference in the tendency between the MAV/06 vaccine group and the Oka vaccine group, indicating a long-term persistence of antibodies of the MAV/06 vaccines would be similar to that of the Oka vaccine.⁷⁹

• Cell-mediated immunity (CMI)

  CMI is known to play a crucial role in regulating VZV and providing protection against additional VZV infections. Therefore, it was investigated whether CMI is induced after MAV/06 vaccination using a non-clinical animal model, and the results confirmed the induction of CMI through a Th1 cell-mediated response.⁸¹

• Cross-reactive humoral immunity

  VZV exhibits genetic variation regionally, but currently licensed varicella vaccines are all developed based on clade 2 strains.^4,7,82 Studies have investigated whether antibodies generated from Oka varicella vaccines elicit immune responses against different genotypes of varicella viruses.⁸³ Similarly, research has been conducted to assess cross-reactivity of antibodies generated after MAV/06 vaccination with varicella viruses of different clades, using both animal and human sera.^81,84 The findings indicate that antibodies generated after MAV/06 vaccination show effective immune responses against varicella viruses of different clades (clades 1, 3, and 5), including wild-type clade 2 viruses, demonstrating high and similar FAMA antibody titers across different clades.⁸⁴

Table 10.

Immunogenicity of MAV/06 vaccines in clinical trials.

Clinical trial (year)	Cohort	SCR1 No, of subjects achieved/ No. of total subjects (%)	FAMA GMT2 (95% CI)
1994*40	300 PFU3 500 PFU 1,000 PFU 1,500 PFU	6/6(100) 7/7(100) 13/13(100) 6/6(100)	72.0 116.2 83.3 160.9
1995*41	Healthy children Immunocompromised children	161/161(100) 18/18(100)	173.7 111.4
2001*65	9–12 months 1–12 y 13–17 y	100/100(100) 99/100(99) 99/99(100)	741.7 227.6 500.9
2006*78	9–12 months 1–12 y 13–17 y	49/49(100) 62/62(100) 51/52(98.1)	20.6 (15.3, 25.8) 26.4 (19.2, 33.7) 27.0 (18.7, 35.3)
2015**66,67	2,000 PFU 8,000 PFU 25,000 PFU	–	78.8 (44.3, 140.0) 90.5 (53.0, 154.6) 68.6 (41.9, 112.3)
2017**68,69	2,000 PFU 8,000 PFU 25,000 PFU	43/43(100) 41/41(100) 57/57(100)	85.5 (63.7, 114.9) 109.9 (88.6, 136,5) 65.6 (51.4, 83.6)
2018**42,68,69	BARYCELA VARIVAX	234/239(97.9) 237/239(99.2)	74.2 (65.0, 84.8) 112.7 (99.1, 128.1)
2024**70,71	12–24 months 2–12 y	--	69.9 (63.7, 76.7)*** 126.5 (95.0, 168.5)***

¹SCR: Sero Conversion Rate (≥1:4), ²GMT: Geometric Mean Titer, ³PFU: Plaque Forming Unit, *Varicella Vaccine-GCC inj., **BARYCELA inj., ***gpELISA GMT.

Table 11.

Comparison of seropositivity between MAV/06 & Oka vaccines by FAMA test.

	Choi UI et al.[79]	Choi UI et al.[79]	Michalik D. E. et al.[80]	Kim SH et al.[76]
N(M:F)*	26/35(19:16)	22/35(17:18)	113/148	56/67(39:28)
Age range	1–3 y	1–3 y	12–13.4 y	1 y(13–24 months)
Analytical method	FAMA	FAMA	FAMA	FAMA
Vaccine type	MAV/06	Oka	Oka	Oka, MAV/06
Seroprevalence	74%	63%	76%	84%

*Number of seropositive/total; M, male; F, Female.

Effectiveness

After conducting clinical trial on immunogenicity and safety of MAV/06 vaccine in the Philippines in 2001, a follow-up effectiveness study was conducted for 5 y. Out of 299 healthy children enrolled in the previous clinical trial, 163 were able to be observed up to 5 y after the clinical trial. Based on the reviews of the follow-up post-vaccination clinical history and physical examination, none of them followed-up had experienced any significant skin lesions, varicella-like manifestations, or evidence of clinical varicella during the 5 y of post-vaccination, indicating 100% protection over the follow-up period.⁷⁸

In addition, two separate groups of Korean researchers investigated changes in the varicella epidemiology in Korean populations before and after the introduction of a one-dose universal varicella vaccination program in 2005. They reported that varicella incidence significantly decreased by 60–67%, and the peak age of varicella occurrence also shifted toward older ages.^85–87 Furthermore, according to a recent study,⁸⁸ the incidence rate of complicated varicella cases among Korean children significantly (96%) decreased from 137 per 100,000 persons in 2010 to 6 per 100,000 persons in 2021. Considering that MAV/06 vaccine was predominantly distributed in Korea during this period, all of the above results indirectly support the effectiveness of the MAV/06 vaccine in Korean populations.

In a retrospective birth cohort study in 2011 in Korea where the vaccine coverage was higher than 95%, the incidence rate of break-through varicella cases in the cohort that received a single dose of MAV/06 vaccine was 27.1 per 1000 person-years during a follow-up period of 6 y.^89,90 This rate was similar to the results of other studies conducted in the United States using the vOka-derived vaccine, which reported a range of 21.7–28.3 cases per 1000 person-years.^91–94

GC Biopharma Corp. is currently conducting an effectiveness study with a follow-up period of 6 y in 1000 Korean children who received the BARYCELA vaccine.⁶¹ In addition, it is also conducting a randomized clinical trial on the first and second doses of the BARYCELA vaccine in healthy Thai and Vietnamese children with a follow-up period of 10 y in 474 healthy children (ClinicalTrials.gov ID; NCT07054099). We expect that the on-going studies will provide another good evidence of the effectiveness of the MAV/06 vaccines.

Conclusion

In this study, we conducted a comprehensive review of more than 30 y of accumulated evidence from unpublished and published studies on safety, immunogenicity, and effectiveness of MAV/06 strain vaccines. Our review indicates that in terms of safety, immunogenicity, and effectiveness, MAV/06 varicella vaccines are comparable to vOka strain varicella vaccines, while MAV/06 vaccines have been more cost-effective for low- and middle-income countries than vOka vaccines.

Through various clinical trials and post-marketing studies, including ones on strain-interchangeability, the safety of MAV/06 vaccines, has been confirmed. MAV/06 vaccines appeared to be safer than Oka varicella vaccines in the post-marketing comparison of adverse events (Table 9). However, it should be cautiously interpreted due to differences in pharmacovigilance reporting systems and reporting behaviors of healthcare professionals and consumers between countries. On the other hand, to the best of our knowledge, the recently developed BARYCELA inj. is the first antibiotic-free varicella vaccine in the world, eliminating any safety concerns associated with antibiotics included in varicella vaccines. Outstanding humoral (utilizing the FAMA assay and cross-reactivity test) and cell-mediated immunogenicity of the MAV/06 vaccines has been demonstrated in diverse clinical trials and real-world studies. Also, excellent cross-reactive immunity of MAV/06 vaccine against diverse wild-type varicella viruses (clades 1, 2, 3, and 5) has been demonstrated, based on high and similar FAMA antibody titers across the different clades. Moreover, several post-approval epidemiological studies in Korean and Filipino children have supported the effectiveness of MAV/06 vaccines.

There are a few limitations in this study. First, the evidence of effectiveness of MAV/06 vaccines summarized in this article has been based on observational cohort studies. There is yet no evidence for the effectiveness of MAV/06 vaccines from randomized clinical trials. We expect that the currently on-going (ClinicalTrials.gov ID; NCT07054099) and future trials will fill the knowledge gap. Second, 10 unpublished official documents as well as peer-reviewed published articles about MAV/06 vaccines were included in our review. Out of the ten unpublished documents, two were latest PBRER reports,^48,61 three were market authorization documents,^58–60 and five were reports of clinical studies.^{65,66,68,71,78} We think that the unpublished official documents, which carry minimal risk of bias, provided additional valuable information on the characteristics, safety, and immunogenicity of MAV/06 vaccines. All of the unpublished official documents will be available on request to the authors. Third, in this study, we reviewed and discussed the evidence of safety, immunogenicity, and effectiveness of one-dose MAV/06 varicella vaccination. However, such evidence for two-dose MAV/06 varicella vaccination remain to be tested and confirmed in future clinical studies.

MAV/06 varicella vaccines, which are developed by GC Biopharma Corp., have been distributed worldwide with more than 30 million doses over the past 30 y, ensuring stable vaccine supply to numerous countries. Varicella vaccine administration is the most effective method for preventing chickenpox. Economic barriers can increase inequality in vaccination, which highlights the importance of distributing cost-effective varicella vaccines. We expect that MAV/06 vaccines as cost-effective varicella vaccines make a significant contribution to improving global public health and health equality in children.

Biographies

Younchul Shin received his Ph.D. in Virology from the Department of Biochemistry at Yonsei University. He joined the Mogam Institute as a Senior Researcher in 2011 and he is a Head of Regulatory Affairs II Team from Regulatory Science & Product Development Division at GC Biopharma Corp. since 2016. Dr. Shin has played a key leadership role in the development of various GC Biopharma vaccines, notably serving as Project Leader in the successful regulatory approval of GC’s seasonal influenza and varicella vaccines. Currently, he oversees vaccine development as the Principal Investigator of both the Vaccine Innovative Technology Alliance Korea (VITAL-Korea) and the mRNA Vaccine Development Support Project for Pandemic Preparedness from KDCA (Korea Disease Control and Prevention Agency).

BongKyoo Choi serves as the Head of the AI & Data Science Center in the Regulatory Science & Product Development Division at GC Biopharma Corp. He is also an Adjunct Professor in the Department of Biohealth Regulatory Science at Sungkyunkwan University, Republic of Korea. His research interests include pharmacoepidemiological studies, investigating the safety and effectiveness of vaccines and immunotherapeutics using real-world data to support regulatory decision-making.

Funding Statement

This research received no external funding.

Disclosure statement

All authors are employees of GC Biopharma Corp. Involvement of GC Biopharma Corp. employee did not compromise the scientific integrity of this work.

Ethics statement

This review paper does not involve human participants. All studies of MAV/06 vaccines included and introduced in this paper were reviewed and approved by an ethics committee at each study site.