Table 1.

Main vaccine candidates that are in phases 2/3 of clinical trials or have been approved for emergency use to date

Platform	Description	Advantages	Disadvantages	References
Inactivated	Viral pathogens inactivated by chemical agents or radiation	Easy to prepare Safer in relation to attenuated vaccines.	Variable Efficacy Need for large-scale cultivation of highly pathogenic organisms under biosafety level 3 (BSL3) Requirement of strong protocols in quality control
Vaccine Candidates:	Sinovac (CoronaVac) Sinovac Life Sciences and Butantan Institute. China/Brazil Type of vaccine: inactivated virus inoculated in African green monkey kidney cells (Vero cells). Antigen: SARS-CoV-2 (CN02 strain) Number of doses: 2; Dosing schedule: 0, 14 days; Administration Route: IM Phase: III; Age range (years): 18 or older Description: Good tolerance to low, medium, and high dose groups. No serious adverse event related to the vaccine was reported. Both the seroconversion and the level of GMT for elderly volunteers were comparable to adult age groups between 18 and 59 years old. The World Health Organization gave emergency authorization to the vaccine on June 2021. Currently, this vaccine is approved in 26 countries. Efficacy: 50,65% in Brazil trial and 91,25% in Turkey trial			8
	Inactivated novel coronavirus vaccine Wuhan Institute of Biological Products/Sinopharm. China Type of vaccine: inactivated virus cultivated in a qualified Vero cell line. Antigen: SARS-CoV-2 (WIV04 strain, National Genomic Data Center of the Chinese Academy of Science accession No. SAMC133237, and GenBank accession number MN996528) Number of doses: 2; Dosing schedule: 0, 21 days; Administration Route: IM Phase: III; Age range (years): 18 or older Partial Results: The results in phases I and II showed that the inactivated vaccine was demonstrated immunogenicity and well-tolerated in all dose groups under different injection procedures with no vaccine-related serious adverse events. Efficacy and adverse event data in phase III studies have been released. Currently, China is the only country that has approved the use of this vaccine for general use. Efficacy: 72,8%			9
	Inactivated novel coronavirus vaccine (BBIBP-CorV) Beijing Institute of Biological Products/Sinopharm. China Type of vaccine: inactivated virus cultivated in a qualified Vero cell line. Antigen: strain 19nCoV-CDC-Tan-HB02 (HB02) Number of doses: 2; Dosing schedule: 0, 21 days; Administration Route: IM Phase: III; Age range (years):18 to 85 Partial results: In the phase I/II studies, the inactive vaccine BBIBP-CorV administered as a two doses immunization was safe and well-tolerated, allowing people generate antibodies against the coronavirus. A robust humoral response was observed in 100% of vaccine receptors. In December of 2020, Sinopharm announced vaccine approval. The company has yet to publish the detailed results of its Phase III trial. The vaccine is currently approved for emergency use in more than forty countries, of which three have released definitive registration: Bahrain, China, and the United Arab Emirates. Efficacy: 78.1%			10
Non-replicant recombining viral vector	Unrelated virus, designed to encode the target gene of the pathogen. Viral vectors can be replicating or non-replicating	Induces high cell and humoral immune responses	Possible preexisting immunity against vector Virulence reversion risk Limitations to increase production
Vaccine Candidates:	AZD1222 (ChAdOx1-S, Vaxzevria, or Covishield in India) University of Oxford/AstraZeneca. The United Kingdom Type of vaccine: Simian adenoviral vaccine vector. Antigen: Spike protein; Number of doses: 1; Administration Route: IM Phase: III; Age range (years): 18 to 55 Partial Results: This vaccine showed in phase I/II studies an acceptable safety profile and increased antibody responses with homologous reinforcement. These results allowed the evaluation on a large scale of this vaccine candidate in a phase III program. The vaccine has a register of approval in Brazil and a license for emergency use in over 70 countries. countries. Efficacy: 76% in a U.S. study			11–13
	Ad5-nCoV (or Convidecia) CanSino Biological Inc./Beijing Institute of Biotechnology. China Type of vaccine: Adenovirus Type 5 vector. Antigen: Spike protein Number of doses: 1; Administration Route: IM Phase: III; Age range (years): 18 or older Partial Results: The researchers published promising results from a Phase I safety trial. The phase II trial was started before the full analysis of the data from the phase I study was available. The COVID-19 vaccine with Ad5 vector in 5 × 1010 viral particles showed to be secure in phase II essays and induced significant immune responses in most receptors after a single immunization dose. In this study, most reactions reported post-vaccination were mild or moderate. Starting in August 2020, CanSino began running Phase 3 trials in some countries. In February 2021, China announced the approval of the CanSino vaccine for general use, and four other countries have approval for emergency use for this vaccine. Efficacy: 65,28%			14,15
	Gam-COVID-Vac (or Sputnik V) Gamaleya Research Institute Janssen. Russia Type of vaccine: Recombinant adenovirus type 26 (rAd26) (component I) + recombinant adenovirus type 5 (rAd5) (component II). Antigen: SARS-CoV-2 full-length spike glycoprotein coding gene Number of doses: 2; Dosing schedule: 0 (component I), 21 (component II) days; Administration Route: IM Phase: III; Age range (years): 18 or older Partial Results: The results published of phase I/II non-randomized studies of a heterologous prime-boost COVID-19 vaccine based on rAd26 and rAd5 vectors are safe and immunogenic in healthy adults. All reported adverse events were mostly mild. The results of the phase III trial show that the vaccine-induced robust humoral (n = 342) and cellular (n = 44) immune responses in all age groups. The vaccine is currently approved for emergency use in more than 60 countries. Efficacy: 91.6%			16,17
	Ad26.COV2.S (or JNJ-78436735) Janssen Pharmaceutical Companies of Johnson & Johnson. USA Type of vaccine: Ad26.COV2.S (a non-replicating adenovirus 26 based vector). Antigen: The stabilized pre-fusion spike protein of SARS-CoV-2 Number of doses: 2; Dosing schedule: 0, 56 days; Administration Route: IM Phase: III; Age range (years): 18 or older Partial results: Phase I/II tests showed satisfactory results in the safety profile and immunogenicity after only a single dose. The results of phase III tests were also satisfactory. This vaccine is currently approved for emergency use in more than 40 countries. Efficacy: 72% in The United States, 68% in Latin America, 64% in South Africa			18
Subunit vaccines	Antigen components of the target protein produced in the laboratory	High-scale production Safety	Low immunogenicity and may require the use of adjuvants or repeated doses High cost
Vaccine Candidates:	SARS-CoV-2 rs/NVX-CoV2373 Novavax. USA Type of Vaccine/antigen: Full-length recombinant SARS CoV-2 Spike glycoprotein nanoparticle vaccine adjuvanted with Matrix MTM Number of doses: 2; Dosing schedule: 0, 21 days; Administration Route: IM Phase: III; Age range (years): 18 to 84 Partial Results: Phase I/II essays showed that the NVX-CoV2373 showed acceptable safety results and induced high immune responses. The Matrix-M1 adjuvant induced responses of CD4 + T cells that were influenced toward a Th1 phenotype. The general reactogenicity was practically absent or mild, and the second vaccinations were neither suspended nor delayed due to reactogenicity. Novavax’s vaccine is one of several being tested in an Oxford study that gauges how well alternating doses can boost immunity. The vaccine is in phase III clinical trial in some countries. This vaccine is not yet approved and the results are in progress. Efficacy: 96% against original coronavirus; 86% against B.1.1.7 and 49% against B.1.351			19
DNA vaccines	DNA encoding the target antigen	Rapid large-scale vaccine construction and production Good cost-benefit, reproducible, noninfectious	It naturally has low immunogenicity It may require certain approaches for administration as electroporation devices and the use of adjuvants
Vaccine Candidates:	INO-4800 Inovio Pharmaceuticals/ International Vaccine Institute Type of vaccine: DNA plasmid + EP (CELLECTRA® 2000 device). Antigen: plasmid pGX9501 expressing a sequence of the SARS-CoV-2 full-length spike glycoprotein Number of doses: 2; Dosing schedule: 0, 28 days; Administration Route: ID Phase: II–III (combined phases); Age range (years): 18 to 64 Partial Results: The initial data from a Phase I study did not reveal any serious adverse effects and measured an immune response in all 38 volunteers. INO-4800 was well tolerated and safety data further suggest that the vaccine can be safely boosted since there was no increase in the frequency of side effects after the second dose. Phases II and III are currently being carried out in some countries. Efficacy: data not available			20
	AG0301-COVID19 Osaka University/ AnGes, Inc./ Takara Bio. Japan Type of vaccine: DNA plasmid vaccine + Adjuvant; Antigen: spike protein Number of doses: 2; Dosing schedule: 0, 14 days; Administration Route: IM Phase: II–III (combined phases); Age range (years): 20 to 65 Partial Results: study not reported Efficacy: data not available
mRNA vaccines	The mRNA encoding the target antigen. It is usually complexed with lipids or polymer-based nanoparticles	It is easy, fast, scalable, and economical to produce Once in the cytoplasm of the cell, the vaccine is ready for translation and does not need to reach the nucleus	It naturally has low immunogenicity and presents high instability It may require specific storage conditions at very low temperatures
Vaccine Candidates:	mRNA-1273 Moderna/NIAID. USA Type of vaccine: LNP-encapsulated mRNA. Antigen: Lipid-nanoparticle (LNP)–encapsulated mRNA vaccine expressing the prefusion-stabilized spike glycoprotein Number of doses: 2; Dosing schedule: 0, 28 days; Administration Route: IM Phase: III; Age range (years): 18 or older Partial Results: In the initial phase I/II trials, the mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. In addition, in a small study involving older adults, the adverse events associated with the mRNA-1273 vaccine were mostly mild or moderate. In the phase III trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. The vaccine is currently approved for use in Switzerland and emergency use in more than twenty countries. Efficacy: More than 90%			21,22
	BNT162b1/BNT162b2 (or Comirnaty, and tonizameran) BioNTech/Fosun Pharma/Pfizer. Germany/USA Type of vaccine: 3 LNP-mRNAs. Antigen: Lipid nanoparticle–formulated with SARS-CoV-2 full-length spike protein Number of doses: 2; Dosing schedule: 0, 28 days; Administration Route: IM Phase: III; Age range (years): 16 or older Partial Results: Phase I/II essays show two versions of an mRNA vaccine. The version BNT162b2 was associated with a lower incidence and severity of systemic reactions than that of BNT162b1, particularly in the elderly. In younger and older adults, both vaccine candidates produced SARS-CoV-2 GMT depending on similar doses, which were similar or superior to the geometric mean titer of a sample panel with convalescent SARS-CoV-2 serum samples. The data presented in the phase III trial showed that a two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in subjects 16 years of age or older. The safety profile of BNT162b2 was characterized as mild-to-moderate, and the incidence of serious adverse events was low, with similarity in the vaccine and placebo groups. The vaccine is currently approved for use in Bahrain, Brazil, New Zealand, Saudi Arabia, and Switzerland. The emergency use of the vaccine covers more than 50 countries. Efficacy: 91,3%			23–28
	CVnCoV Curevac. Germany Type of vaccine: mRNA. Antigen: SARS-CoV-2 spike protein Number of doses: 2; Dosing schedule: 0, 28 days; Administration Route: IM Phase: III; Age range (years): 18 or older Partial Results: study not reported Efficacy: data not available

IM = intramuscular; EP = electroporation; ID = intradermic; GMT = Geometric Means Titer from detected antibodies.