Abstract
Purpose
The coronavirus disease 2019 (COVID-19) pandemic led to the rapid development of vaccines to control the spread of infection. The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Sinopharm BIBP vaccine was introduced in the United Arab Emirates (UAE) and registered by the Ministry of Health and Prevention before the final data of the phase III clinical trial was released. Hence, a post-authorization effectiveness and safety study was required to evaluate the effectiveness and safety profile of the vaccine.
Materials and Methods
An observational Phase IV study was conducted in Sheikh Khalifa Medical City, UAE, for 18 months. The effectiveness of the BIBP vaccine was evaluated in individuals who received at least the first 2 doses and those who received the full vaccine course (with booster dose) based on immunogenicity assessment of anti-SARS-CoV-2 antibodies and protection against COVID-19.
Results
About 96% of the participants showed positive results for the neutralizing antibody and anti-S antibody against the SARS-CoV-2, 14 days after the second dose of the vaccine. The participants showed similar positive results after the booster vaccine, and the antibodies remained at that level at the one-year follow-up. Only 16 participants who received at least one dose of the vaccine experienced COVID-19. Safety outcomes showed that all serious adverse events reported were unrelated to the vaccine. No death was reported in this study period.
Conclusion
The inactivated BIBP Sinopharm vaccine proved safe and effective in protecting against COVID-19.
Keywords: SARS-CoV-2; Vaccines, Inactivated; COVID-19 vaccine
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic is considered one of the greatest threats that humankind has witnessed in this century. Developing a safe and effective vaccine and implementing an effective vaccination program worldwide was the need of the hour to return to pre-pandemic normalcy [1]. The COVID-19 infection was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and the infections were first identified in Wuhan, China, towards the end of 2019 [2].
As per the World Health Organization COVID-19 dashboard, SARS-CoV-2 has infected more than 774.2 million individuals, and the death toll is more than 7 million people globally till January 2024 and counting [2]. While the SARS-CoV-2 infection was widespread, countries worldwide adopted various mitigation measures to prevent the spread of infection. However, people who did not acquire the infection had no immunity against the disease, ironically making them more vulnerable to future waves of infections with more virulent forms of the SARS-CoV-2 virus [3,4,5].
Novel coronavirus vaccine development was urgently required to control the emergence of COVID-19 and reduce its infection-related morbidity and mortality [6]. Vaccine platforms were categorized into nucleic acid-based (DNA or mRNA) vaccines, protein subunit vaccines, live attenuated viruses, inactivated or killed viruses, recombinant viral-vectored vaccines, and virus-like particles [7]. Inactivated vaccines may need to be administered multiple times for full efficacy and protective immunity. Adjuvants added to vaccine antigens are required to help trigger an adaptive immune response; however, they may have unfavorable effects in those who have had vaccinations [1,8].
The inactivated SARS-CoV-2 Sinopharm BIBP vaccine comprises virus particles that were culture-grown and then inactivated to lose the disease-inducing capacity but still can elicit an immune response. Among the strains of SARS-CoV-2 that were isolated from throat swabs or bronchoalveolar lavage samples of hospitalized patients during the COVID-19 outbreak, the HBO2 strain has produced the most significant virus yields in Vero cells and showed optimal replication, so it was chosen to develop the BIBP vaccine [9].
Strategies for a safe and efficient COVID-19 vaccination were desperately needed worldwide [1,10]. Over 160 vaccine candidates have been produced because of numerous laboratories and companies rushing to develop these vaccines; some of these candidates even entered phase I, II, and III clinical trials within 6 months. Clinical and preclinical vaccine trials have published interim results instantly due to the expedited development procedure. This led to the need for more essential information regarding the durability and quality of vaccine-induced protective immunity [1].
The United Arab Emirates (UAE) Ministry of Health and Prevention (MoHAP) has newly registered the BIBP vaccine before announcing the phase III clinical trial’s final data, as is common with new vaccinations. Accordingly, a Post-Authorisation Effectiveness and Safety Study (PAESS) is required to further evaluate the effectiveness and safety profile of the inactivated SARS-CoV-2 Sinopharm BIBP vaccine in adults.
MATERIALS AND METHODS
Study design and participants
An observational Phase IV study was conducted in Sheikh Khalifa Medical City, Abu Dhabi, UAE, for 18 months, from January 2021 to June 2022, to evaluate the immunogenicity and safety of the BIBP vaccine in subjects aged ≥18 years. The study began after the approval of the Department of Health (DOH) and MoHAP Research Ethics Committee in the UAE (DOH/CVDC/2021/103). Informed consent of the participants was obtained before the study.
A total of 11,369 participants ≥18 years of age were screened; 6 subjects were excluded. The study included participants aged at least 18 years, hemodynamically stable with the cutoff blood pressure to consider vaccination is <160/95 mmHg, participants who planned to start, are already receiving, or have received the BIBP vaccine, and willing and able to provide informed consent. A total of 11,363 participants were enrolled in the study and received the first vaccine on day 0, of which 10,848 subjects received the second vaccine on day 21, and 5,050 participants received the booster vaccine on day 180.
Participants were considered non-eligible if they had any of the following conditions at the time of enrolment: history of severe COVID-19 infection that needed oxygen, history of severe reaction associated with the vaccine, if they have received a live attenuated vaccine within 30 days or killed vaccine within 14 days, if they were pregnant women or planning to be pregnant within 3 months, or lactating women with a baby less than 6 months old. Subjects with the following medical history were also excluded from the study: bleeding disorders, recent history of Guillain Barre Syndrome or transverse myelitis in the past 12 months, active cancer or in remission for less than 6 months, chronic diseases with acute symptoms such as acute symptoms of immunodeficiency, renal failure, liver diseases, lung diseases, diabetes mellitus (DM), coronary artery diseases including hypertension (HTN), bleeding disorders, and central nervous system disorders. Additionally, the following were non-eligible for the second dose and booster vaccine: females with positive urine pregnancy tests, subjects with high fever lasting for 3 days after the previous dose of vaccine, or serious adverse events (SAEs) related to the last dose of the BIBP vaccine.
Following their initial vaccination, all eligible individuals who got the BIBP vaccine were monitored for an entire year to obtain safety and immunogenicity data.
Procedures
During the baseline visit (day 0), participants’ demographics, body weight, height, vital signs, contraception review, and medical history were collected; pregnancy tests and serology were also performed. All participants then received the BIBP vaccine administered as per the manufacturer’s instructions. The inactivated SARS-CoV-2 vaccine developed by Sinopharm, Beijing Institute of Biological Products Co. Ltd is a suspension for intramuscular injection into the deltoid muscle, 0.5 mL/dose per person, containing 4 μg of viral protein. The vaccine was stored at 2°C–8°C and administered in 2 doses; the first was administered on day 0 and the second on day 21. The booster dose for the vaccine was administered on day 180. After each vaccination dose, the investigators followed all participants via tele-consultation and on-site visits. Safety assessment and review of adverse events (AEs) were done on each visit. Serology and immune responses were assessed at baseline before vaccination on day 0 and periodically post-vaccination at days 35, 180, 194, and 360 with 2 main points in time: once on day 35 (14 days after the second vaccine) and on day 194 (14 days after the booster vaccine). Participants were followed up for the development of COVID-19 signs and symptoms; those who developed any of them had to perform a polymerase chain reaction test to confirm the diagnosis and be followed up as per the standard protocol.
Immunogenicity assessment was done for the eligible patients who took at least the primary 2 doses (n=10,848) and those who took the 2 doses and a booster vaccine (n=5,050) (Fig. 1). The following primary parameters were presented with their 95% confidence interval (CI) for the neutralizing antibodies, and binding antibodies: anti-S antibody (i.e., antibodies targeting the Spike protein), and SARS COV-2 IgG (IgG class of antibodies against SARS-CoV-2); percentage of patients with positive and negative test results, geometric mean titers (GMTs), seroconversion rates (SCRs); that were defined as the percentage of subjects with ≥4-fold increase in titers from day 0 just before the vaccine, and geometric mean fold rise (GMFR); with day 0 as the reference, was computed as GMT (day=t)/GMT (day 0) at t=35, 180, 194 and 360. Anti-S antibodies were quantified using the QuantiVac ELISA, and neutralizing antibodies were measured by an inhibition assay. Additionally, the SARS-CoV-2 IgG antibodies were measured by both Chemiluminescent Microparticle Immunoassay and Chemiluminescent Immunoassay.
Fig. 1. Immunogenicity population flow chart.
Safety assessment was performed on all enrolled participants who received at least one dose of BIBP vaccine (n=11,369) (Fig. 2). The incidence and percentage of participants with solicited local and systemic AEs from day 0 after the immunization were computed. This was done over different periods throughout the study: period 1 is day 0 to day 7 (after the first vaccine), period 2 is day 21 to day 28 (after the second vaccine), Period 3 is day 35 to 155 (between the second and booster vaccines), and period 4 is day 180 to day 360 (after booster vaccine). At every study visit, participants were asked standard questions to elicit any medically related changes in their well-being. They were also asked if they had been hospitalized, had any accidents, or had any COVID-19 signs and symptoms.
Fig. 2. Safety population flow chart.
All AEs and SAEs were collected and reported via follow-up tele-consultation and on-site visits for the entire study duration from the time of vaccination of the first dose until completion of the last study-related procedure.
Sample size
The estimated sample size was 8,000 participants to be able to estimate the incidence rate of a 4-fold growth rate mainly at days 35 and 194 but also at any time point to within a margin of error of at most ±1.1% using a 95% CI with the addition of 40% loss to follow-up, the total sample size was determined to be 13,500 participants. Moreover, this sample size allows the estimation of the incidence of side effects to within a margin of error of at most ±0.5% for those with an incidence of 5% or less, to within ±0.225% for an incidence of 1%, and to within ±0.65% for those with incidences of 10% or less using 95% CI.
Study outcomes
The primary outcome measures for immunogenicity were assessed during the study as follows:
• The 4-fold increase rate, GMT, and geometric mean of the increase from baseline of anti-SARS-CoV-2 neutralizing antibody in 14 days after the full course of immunization versus baseline.
• The incidence of confirmed SARS-CoV-2 disease and the epidemiological protection rate of inactivated SARS-CoV-2 vaccine against SARS-CoV-2 disease.
The secondary outcome measure was the safety of the inactivated SARS-CoV-2. The outcome measures for safety were the incidence of AEs after each dose of vaccination, the incidence of SAEs from the first dose to one month after the last dose of vaccination, and the severity of confirmed SARS-CoV-2 disease.
Statistical analysis
A statistical report was prepared using IBM-SPSS (version 26, IBM Corp., Armonk, NY, USA), and statistical significance was set at the 5% level. For immunogenicity data analysis, the neutralizing antibodies, anti-S antibody, and serum IgG, the following data were summarized: percentage of patients with positive and negative test results at each time point: GMTs, 2-sided 95% CIs, GMFR along with the corresponding 2-sided 95% CIs. For SCRs, the rate in percent and the corresponding 2-sided exact binomial 95% CIs were calculated using the Clopper-Pearson method.
The incidence density was computed as the number of confirmed COVID-19 cases during the effective follow-up period/number of observation years of all vaccinated subjects. Its 95% CI was computed using the Poisson distribution. Median time to incidence was computed using the Kaplan-Meier method, where participants lost to follow-up or finished the study with no incidence of COVID-19 were considered censored at the time of the last follow-up, and the mean time to COVID-19 infection replaced the median as it was not estimable. In addition, the percentages of participants free from COVID-19 at day 180 and day 360 were computed along with their 95% CI.
Safety parameters were summarized using descriptive statistics. The number and percentage of participants with AE and SAEs were summarized by MedDRA system organ class and preferred term, including classification/description, relationship to the study vaccine, and the outcomes of the SAE. Additional summaries showed the number and percentage of participants with AE classified by severity and relationship to the study vaccine. For the main parameters, 95% CIs were calculated.
RESULTS
Population characteristics
A total of 11,363 participants of eligible participants who satisfied the inclusion criteria were recruited for the study. The average age of participants was 36.1 years, ranging between 18 and 87 years. Approximately 3-quarters of the participants were males, and the vast majority (95.4%) were non-nationals. Indian participants made up the largest group (36.8%), followed by the Filipinos (13.4%) and the Pakistanis (11.5%). Participants had an average body weight of 74.6 kg with an average body mass index of 26.2 kg/m2. Most of the participants (90.8%) showed no past medical history. About 9% of the participants reported ongoing chronic medical history: DM (5.4%), HTN (4.2%), and asthma (1.5%). Other variables, including other diseases and vital signs, are reported in Table 1.
Table 1. Baseline characteristics of study participants.
| Characteristics | Total study participants (n=11,363) | ||
|---|---|---|---|
| Age (yr) | |||
| Mean ± SD | 36.1±8.7 | ||
| Min–Max | 18–87 | ||
| Age groups (yr) | |||
| 18–29 | 2,698 (23.7) | ||
| 30–40 | 5,513 (48.5) | ||
| 41–87 | 3,152 (27.7) | ||
| Sex | |||
| Male | 8,682 (76.4) | ||
| Female | 2,681 (23.6) | ||
| National | |||
| Yes | 528 (4.6) | ||
| No | 10,835 (95.4) | ||
| Nationality | |||
| Indian | 4,183 (36.8) | ||
| Filipino | 1,517 (13.4) | ||
| Pakistani | 1,303 (11.5) | ||
| Emirati | 528 (4.6) | ||
| Egyptian | 508 (4.5) | ||
| Nepalese | 450 (4) | ||
| Jordanian | 389 (3.4) | ||
| Bangladeshi | 319 (2.8) | ||
| Other | 2,166 (19.1) | ||
| Weight (kg) | |||
| Mean ± SD | 74.6±14.7 | ||
| Min–Max | 33–164 | ||
| Height (cm) | |||
| Mean ± SD | 168.5±8.7 | ||
| Min–Max | 130–210 | ||
| BMI (kg/m2) | |||
| Mean ± SD | 26.2±4.4 | ||
| Min–Max | 14.3–78.1 | ||
| Temperature (℃) | |||
| Mean ± SD | 36.4±0.2 | ||
| Min–Max | 35.8–37 | ||
| Systolic blood pressure (mmHg) | |||
| Mean ± SD | 130±10.8 | ||
| Min–Max | 90–160 | ||
| Diastolic blood pressure (mmHg) | |||
| Mean ± SD | 80.9±6.1 | ||
| Min–Max | 50–95 | ||
| Pulse rate (beats/min) | |||
| Mean ± SD | 73.8±8.8 | ||
| Min–Max | 54–140 | ||
| Respiratory rate (breaths/min) | |||
| Mean ± SD | 18.2±0.8 | ||
| Min–Max | 15–80 | ||
| Medical history | |||
| No | 10,320 (90.8) | ||
| Yes | 1,043 (9.2) | ||
| DM | 619 (5.4) | ||
| HTN | 473 (4.2) | ||
| Asthma | 176 (1.5) | ||
| Neoplasm | 88 (0.8) | ||
| Chronic kidney disease | 58 (0.5) | ||
| Gout | 39 (0.3) | ||
| Heart Diseases | 35 (0.3) | ||
| Immunodeficiencies | 19 (0.2) | ||
| Respiratory diseases | 9 (0.1) | ||
| Transplant patients | 6 (0.1) | ||
| Others | 10 (0.1) | ||
Values are presented as number (%).
SD, standard deviation; BMI, body mass index; DM, diabetes mellitus; HTN, hypertension.
Immunogenicity assessment
Among the study participants who took at least the first 2 doses of the vaccine, about 30% had positive results for the neutralizing antibody and anti-S antibody tests at baseline. At day 35 (14 days after the second vaccine), the percentage increased to above 96%. After a 6-month interval, on day 180, about 70% of the study participants still had positive results for both tests. On day 194, those rates increased to about 96% and remained at those levels for the 1-year follow-up on day 360. Among the participants who did the SARS CoV-2 IgG test, about 22.2% were positive on day 35, 38.2% were positive on day 180, 74.3% were positive on day 194, and 73.3% were positive on the follow-up of the participants on day 360. Similar results were seen among the participants who received all vaccine doses (the first 2 doses and booster vaccine), as demonstrated in Table 2. After the second vaccine dose, positive results for the neutralizing antibody and anti-S antibody tests increased to over 96%, and after the booster shot, to above 98%. These results were maintained at about 96% on day 360 at the follow-up.
Table 2. Immunogenicity test results of the study participants.
| Characteristics | Neutralizing antibody test results | Anti-S antibody test results | SARS CoV-2 IgG test results | ||
|---|---|---|---|---|---|
| Participants who received at least the first 2 doses of the vaccine (n=10,848) | |||||
| Baseline | |||||
| Positive | 3,095 (28.8) | 3,260 (30.3) | |||
| Negative | 7,668 (71.2) | 7,503 (69.7) | |||
| No test | 85 | 85 | |||
| Day 35 | |||||
| Positive | 8,189 (96.6) | 8,001 (96.3) | 6 (22.2) | ||
| Negative | 291 (3.4) | 309 (3.7) | 21 (77.8) | ||
| No test/follow-up | 2,368 | 2,538 | 10,821 | ||
| Day 180 | |||||
| Positive | 3,821 (70.6) | 3,863 (71.5) | 2,057 (38.2) | ||
| Negative | 1,593 (29.4) | 1,541 (28.5) | 3,328 (61.8) | ||
| No test/follow-up | 5,434 | 5,444 | 5,463 | ||
| Day 194 | |||||
| Positive | 2,722 (95.9) | 2,716 (96.0) | 2,097 (74.3) | ||
| Negative | 115 (4.1) | 112 (4.0) | 724 (25.7) | ||
| No test/follow-up | 8,011 | 8,020 | 8,027 | ||
| Day 360 | |||||
| Positive | 1,716 (96.2) | 1,721 (96.5) | 1,306 (73.3) | ||
| Negative | 68 (3.8) | 62 (3.5) | 476 (26.7) | ||
| No test/follow-up | 9,064 | 9,065 | 9,066 | ||
| Participants who received the first 2 doses and the booster dose of the vaccine (n=5,050) | |||||
| Baseline | |||||
| Positive | 1,611 (32.2) | 1,696 (33.9) | |||
| Negative | 3,394 (67.8) | 3,309 (66.1) | |||
| No test | 45 | 45 | |||
| Day 35 | |||||
| Positive | 4,270 (97.4) | 4,172 (96.4) | 1 (20.0) | ||
| Negative | 113 (2.6) | 158 (3.6) | 4 (80.0) | ||
| No test/follow-up | 667 | 720 | 5,045 | ||
| Day 180 | |||||
| Positive | 3,411 (71.8) | 3,457 (72.8) | 1,849 (39.1) | ||
| Negative | 1,340 (28.2) | 1,293 (27.2) | 2,878 (60.9) | ||
| No test/follow-up | 299 | 300 | 323 | ||
| Day 194 | |||||
| Positive | 2,582 (98.7) | 2,575 (98.5) | 2,023 (77.8) | ||
| Negative | 35 (1.3) | 40 (1.5) | 576 (22.2) | ||
| No test/follow-up | 2,433 | 2,435 | 2,451 | ||
| Day 360 | |||||
| Positive | 1,715 (96.2) | 1,721 (96.5) | 1,306 (73.3) | ||
| Negative | 68 (3.8) | 62 (3.5) | 476 (26.7) | ||
| No test/follow-up | 3,267 | 3,267 | 3,268 | ||
Values are presented as number (%).
SARS CoV-2, severe acute respiratory syndrome coronavirus 2; IgG, immunoglobulin G.
Results of the neutralizing antibody, anti-S antibody, and SARS CoV-2 IgG tests in participants who got at least the first 2 vaccine doses and participants who got the 3 vaccines are demonstrated in Table 3. As for the titers, GMT for neutralizing antibodies and anti-S antibodies increased on day 35, 14 days after the second vaccine, compared to the baseline on day 0, then dropped on day 180, increased on day 194, 14 days after the booster vaccine, and sustained at this high level on the one-year follow up on day 360. The SCRs of both antibodies were elevated on day 35, dropped on day 180, increased on day 194, and maintained this level on day 360. These changes were also reflected in the GMFR. Only a few participants had IgG test results on day 35, so day 180 was used as the baseline, and the immunogenicity parameters showed the same trend.
Table 3. Results of the neutralizing antibody, anti-S antibody, and SARS CoV-2 IgG tests.
| Characteristics | GMT (95% CI) | SCR (95% CI) | GMFR (95% CI) | ||
|---|---|---|---|---|---|
| Neutralizing antibody (inhibition) test result | |||||
| At least 2 doses of the vaccine | |||||
| Day 0 | 7.5 (7.3–7.8) | - | - | ||
| Day 35 | 66.1 (65.3–67) | 59.1% (58.0%–60.1%) | 8.6 (8.3–9) | ||
| Day 180 | 39.3 (38–40.6) | 46.2% (44.9%–47.6%) | 4.7 (4.5–4.9) | ||
| Day 194 | 78.4 (76.9–80) | 61.1% (59.3%–62.9%) | 10.1 (9.4–10.8) | ||
| Day 360 | 78.6 (76.8–80.5) | 60.0% (57.7%–62.3%) | 9.9 (9.1–10.7) | ||
| All 3 vaccines | |||||
| Day 0 | 8.5 (8.1–8.9) | - | |||
| Day 35 | 68.9 (67.7–70) | 56.9% (55.4%–58.4%) | 8.1 (7.7–8.5) | ||
| Day 180 | 40.3 (38.9–41.7) | 44.8% (43.3%–46.2%) | 4.5 (4.3–4.8) | ||
| Day 194 | 84.3 (83.3–85.3) | 61.6% (59.7%–63.5%) | 10.6 (9.9–11.4) | ||
| Day 360 | 78.6 (76.8–80.5) | 60.0% (57.7%–62.3%) | 9.9 (9.1–10.7) | ||
| Anti-S antibody (QuantiVac) test result | |||||
| At least 2 doses of the vaccine | |||||
| Day 0 | 15.0 (14.6–15.4) | - | - | ||
| Day 35 | 239.8 (234.3–245.4) | 79.0% (78.1%–79.8%) | 15.6 (15.1–16.1) | ||
| Day 180 | 124.4 (118.3–130.9) | 53.2% (51.8%–54.5%) | 7.8 (7.4–8.2) | ||
| Day 194 | 433.8 (414–454.5) | 77.4% (75.8%–79%) | 27.5 (25.6–29.7) | ||
| Day 360 | 507.9 (477.7–540) | 84.4% (82.6%–86%) | 30.4 (27.8–33.2) | ||
| All 3 vaccines | |||||
| Day 0 | 17.0 (16.3–17.8) | - | - | ||
| Day 35 | 253.3 (245.3–261.5) | 78.4% (77.2%–79.7%) | 14.9 (14.2–15.6) | ||
| Day 180 | 131.2 (124.4–138.3) | 53.0% (51.6%–54.4%) | 7.7 (7.2–8.1) | ||
| Day 194 | 490.3 (470.2–511.3) | 79.1% (77.5%–80.7%) | 29.8 (27.7–32.2) | ||
| Day 360 | 507.9 (477.7–540) | 84.4% (82.6%–86%) | 30.4 (27.8–33.2) | ||
| SARS CoV-2 IgG test result | |||||
| At least 2 doses of the vaccine | |||||
| Day 35 | - | - | - | ||
| Day 180 | 0.6 (0.6–0.7) | - | - | ||
| Day 194 | 2.3 (2.2–2.3) | 34.6% (32.8%–36.5%) | 3.4 (3.2–3.6) | ||
| Day 360 | 2.8 (2.6–3) | 47.3% (44.8%–49.8%) | 4.1 (3.7–4.5) | ||
| All 3 vaccines | |||||
| Day 35 | - | - | - | ||
| Day 180 | 0.7 (0.6–0.7) | - | - | ||
| Day 194 | 2.6 (2.5–2.7) | 37.6% (35.7%–39.6%) | 3.8 (3.6–4.1) | ||
| Day 360 | 2.8 (2.6–3) | 47.3% (44.8%–49.8%) | 4.1 (3.7–4.5) | ||
SARS CoV-2, severe acute respiratory syndrome coronavirus 2; IgG, immunoglobulin G; GMT, geometric mean titer; CI, confidence interval; SCR, seroconversion rate; GMFR, geometric mean fold rise.
Incidence of COVID-19 was observed in 16 out of the 11,363 participants who got at least one vaccine. The median follow-up time was 201 days (95% CI, 155–231). The COVID-19 incidence rate was 0.0027 (95% CI, 0.0015–0.0044) per person year. The mean time to infection with COVID-19 for the 16 infected cases was 507.1 days (95% CI, 506.6–507.6) (Fig. 3). Almost all the participants were free from infection on day 180, 99.87% (95% CI, 99.81–99.95), and on day 360, 99.77% (95% CI, 99.63–99.92).
Fig. 3. Time to coronavirus disease 2019 infection in study participants who got at least one dose of the inactivated severe acute respiratory syndrome coronavirus 2 vaccine.
Safety assessment
Safety analyses included all enrolled participants who received at least one dose of the vaccine. On day 7 after the first vaccine, 21.4% of the participants reported at least one AE. A total of 3,070 AEs were reported among 2,144 participants. From which about 2,609 AEs (85%) were treated as outpatients without medication or by self-medication, with 12 hospitalizations reported: one incident for arthralgia, one incident for dyspnea, and 2 incidents for each of cough, fatigue, fever, headache, and myalgia. On day 28, 7 days after the second vaccine, 14.7% of the participants reported at least one AE. There were 2,259 AEs reported among 1,598 participants. Similarly, the vast majority were treated as outpatients without medication or by self-medication (n=2,028. 89.8%). There were 15 hospitalizations reported: 3 incidents for cough, 2 incidents for each of fever, headaches, and sore throat, and one for each incident of diarrhea, dysphagia, dyspnea, fatigue, myalgia, and pruritus. On days 35, 95, 155, and 180, the percentage of patients who experienced at least one AE fell dramatically between 0.4% and 0.8%. Overall, there were 7 hospitalizations: one incident for each acute allergic reaction, cough, arthralgia, body rash, and pruritus, and 2 incidents for dyspnea. Moreover, there was one case of headache with a severity of 5, which was self-medicated and resolved.
On day 187, 7 days after the booster, 12.3% of the participants experienced at least one AE. A total of 862 AEs were reported among 624 participants. Most of those events were either self-treated or not treated (n=776, 90.0%). There were 4 hospitalizations reported, one incident for each of headache, myalgia, weakness in the left arm, and dizziness. Lastly, on days 194 and 360, the percentage of patients reporting at least one AE dropped to 0.18% and 0.06%, respectively, and no participants were hospitalized for AEs during that period. Local and systemic AEs are detailed in Supplementary Table 1.
A total of 70 participants (0.6%) have experienced and reported 75 SAEs (Table 4). The most common SAE was COVID-19 pneumonia (n=16). All SAEs were undoubtedly unrelated to the vaccine, resulting in prolonged hospitalization, but all were resolved. None of the reported SAEs were life-threatening or led to death, permanent or significant loss of function, teratogenicity, or birth defects. No death cases were reported.
Table 4. Examples of SAEs (n=75) reported among the study participants.
| Examples of the reported SAEs | Participants who got at least the first vaccine (n=11,369) |
|---|---|
| Acquired hypermagnesemia | 1 (0.01) |
| Acute appendicitis | 2 (0.02) |
| Acute calculous cholecystitis (laparoscopic cholecystectomy) | 1 (0.01) |
| Acute congestive heart failure | 1 (0.01) |
| Acute cystitis | 1 (0.01) |
| Acute lymphocytic leukaemia | 2 (0.02) |
| Acute pancreatitis | 1 (0.01) |
| Alleged assault | 1 (0.01) |
| Appendicitis | 2 (0.02) |
| Bacteraemia | 1 (10.01) |
| Bilateral acute follicular tonsillitis | 1 (0.01) |
| Bilateral mandibular fractures | 1 (0.01) |
| Bipolar affective disorder | 2 (0.02) |
| Breast cancer surgery | 1 (0.01) |
| Caesarean delivery | 1 (0.01) |
| Compound fracture of middle finger and little finger | 1 (0.01) |
| Contusion of the right lung | 1 (0.01) |
| COVID-19 pneumonia | 16 (0.14) |
| COVID-19 infection | 1 (0.01) |
| Disorder of manganese metabolism | 1 (0.01) |
| Fall trauma | 1 (0.01) |
| Fracture of upper and lower limbs | 1 (0.01) |
| Gastritis | 1 (0.01) |
| Hand injury | 1 (0.01) |
| Haemolytic anaemia (glucose-6-phosphate dehydrogenase) deficiency | 1 (0.01) |
| High-risk pregnancy | 1 (0.01) |
| Hyperemesis gravidarum | 1 (0.01) |
| Intestinal obstruction | 1 (0.01) |
| Laceration of forearm | 1 (0.01) |
| Laceration without foreign body of right forearm | 1 (0.01) |
| Laparoscopic left ureteric re-implantation and changing of stents | 1 (0.01) |
| Left knee contusion | 1 (0.01) |
| LLL pneumonia | 1 (0.01) |
| Major depressive disorder | 1 (0.01) |
| Malaria | 1 (0.01) |
| Migraine | 1 (0.01) |
| Moderate dehydration | 1 (0.01) |
| Motor vehicle collision | 1 (0.01) |
| Myocardial infarction | 1 (0.01) |
| Neck swelling | 1 (0.01) |
| Normal vaginal delivery | 1 (0.01) |
| Pancreatitis | 1 (0.01) |
| Pelvis inflammatory disease | 1 (0.01) |
| Perforated duodenal ulcer | 1 (0.01) |
| Psychosis | 1 (0.01) |
| Right hydrocelectomy | 1 (0.01) |
| Right-sided colon cancer | 1 (0.01) |
| Ruptured globe | 1 (0.01) |
| Sepsis | 1 (0.01) |
| Sickle cell crisis | 1 (0.01) |
| Hb-SS disease with crisis | 1 (0.01) |
| Symptomatic anaemia | 1 (0.01) |
| Syncope | 1 (0.01) |
| Threatened abortion | 1 (0.01) |
| Traumatic subdural hematoma | 1 (0.01) |
| Viral pneumonia | 1 (0.01) |
Values are presented as number (% among participants).
SAE, serious adverse event; COVID-19, coronavirus disease 2019; LLL, left lower lobe.
DISCUSSION
The inactivated SARS-CoV-2 vaccine has undergone phase I–III studies in China and the UAE. The preclinical studies published data from mice, animals, and non-human primate models, showing neutralizing antibodies and protection. Interim information from the clinical studies was released to indicate high antibody conversion rates and the safety of the vaccine recipients [9,11,12]. In this study, we report results on the immunogenicity and safety of the BIBP vaccine evaluation from the PAESS conducted in the UAE. Regarding the immunogenicity and effectiveness, the current study’s findings stated that the vaccine is highly protective, as COVID-19 infection was observed only in 16 out of the 11,363 participants who got at least one vaccine, with an incidence rate of 0.0027 per person year, and almost all the participants were free from infection at day 180 and on the one-year follow-up (day 360).
At day 194, for the participants who had received at least the first 2 vaccine doses, 96% tested positive for anti-S antibodies targeting the virus Spike protein, and 74.3% exhibited SARS-CoV-2 IgG antibodies, suggesting a potential for lasting immunity. These percentages increased to 98.5% and 77.8% for those who received the booster dose. This indicates that the booster dose slightly increased the number of people with detectable IgG antibodies, although the increase was not substantial.
These study findings indicated the BIBP vaccine’s high immunogenicity, which aligned with other comparative studies that proved the vaccine’s effectiveness. Mirahmadizadeh et al. [13] conducted a cohort study in Iran on about 1.9 million participants in which the BIBP vaccine showed 79.9% (95% CI, 79%–80.4%) effectiveness against COVID-19 infection, 71.9% (95% CI, 70.7%–73.1%) effectiveness against hospitalization and 86.1% (95% CI, 84.1%–88.0%) against death. Belayachi et al. [14] conducted a case-control study in Morocco in which the BIBP vaccine effectiveness was 88% up to 1 month after the second dose and 64% on ≥150 days after. In conclusion, the BIBP vaccine offers excellent protection against serious SARS-CoV-2 illness in the real world [14]. A retrospective cohort study was carried out by Silva-Valencia et al. [15] found that the BIBP vaccine effectiveness in reducing COVID-19 infection was 47.6% among healthcare workers in Peru who received 2 vaccine doses. Additionally, Petrović et al. [16] found that the estimated vaccine effectiveness in fully vaccinated elderly persons aged ≥60 years in Serbia was 86.9% (95% CI, 86–87.7).
The prespecified interim analysis of the phase 3 trial in the UAE and Bahrain has proven the efficacy of the inactivated SARS-CoV-2 vaccine, which has induced measurable neutralizing antibodies. At baseline, the GMTs of the neutralizing antibody were 2.3 in the HB02 vaccine group compared to 2.4 in the placebo control group, which increased after the second dose (day 14) to 156 (95% CI, 149.6–162.7) and 2.7 (95% CI, 2.6–2.8) respectively. The SCR was 100.0% in the HB02 group and 2.3% in the placebo control group [12]. In accordance with the mentioned findings, The current study showed positive results for the neutralizing antibody and anti-S antibody tests at baseline, which increased after the second and the booster vaccines and were stable at high levels on the one-year follow-up visit. The antibodies’ GMT and SCR reflected the same elevation. These results are highly predictive indicators of immune protection against COVID-19.
Regarding the safety of the BIBP vaccine, the current study found that 0.6% of the participants experienced SAEs unrelated to the investigational vaccine. After the first vaccine, on day 7, 21.4% of the participants reported at least one AE, which decreased on day 28, 7 days after the second vaccine, to 14.7%, and on day 187, 7 days after the booster vaccine, to 12.3%. In the follow-up visits, the percentage of participants who reported at least one AE fell dramatically between 0.4% and 0.8%. Lastly, on days 194 and 360, it dropped to 0.18% and 0.06% respectively. These results highlighted the high safety profile of the Sinopharm COVID-19 vaccine, which is consistent with other post-authorization studies conducted around the world.
A cross-sectional study was conducted in Jordan by Abu-Hammad et al. [17] to report AEs of AstraZeneca, PfizerBioNTeck, and Sinopharm COVID-19 vaccines among healthcare workers. The study showed that about 18% of participants reported no AEs following the first and second vaccine doses, and no SAEs were reported. The most commonly reported AE following the BIBP vaccine was pain [17]. Saeed et al. [18] conducted a comparative study between 2 doses of the BIBP vaccine and found that fatigue, headache, and injection site pain were the most common AEs reported after the first BIBP vaccine dose, while after the second dose, pain at the injection site, tenderness, lethargy, and fatigue were the most commonly reported AEs. The study also reported zero hospitalization post-vaccination with the BIBP vaccine [18]. In addition, Al Khames Aga et al. [19] in the study of vaccine safety of Pfizer, AstraZeneca, and Sinopharm COVID-19 vaccination, all 3 vaccines had a good safety profile, with the Sinopharm vaccination exhibiting a lower prevalence of AEs than the other 2.
In the current study, no death was reported throughout the study period; however, the study lacked sufficient power to evaluate the BIBP vaccine’s effectiveness against COVID-19-related mortality.
The inactivated SARS-CoV-2 vaccine from Sinopharm/BIBP provided reasonable immunogenicity and effectiveness in protecting against COVID-19 infection and a high safety profile.
Footnotes
Funding: The funding for the study was obtained from Cogna Technology Solutions LLC, Abu Dhabi, United Arab Emirates and has no undue influence on the scientific content of the manuscript.
Conflict of Interest: The authors declared no conflict of interest. Sinopharm has sponsored PDC CRO to write the manuscript and has no undue influence on the scientific content of the manuscript. Medical writing support was provided by Yasmin Abd El Ghany and Dina Reda of PDC CRO.
SUPPLEMENTARY MATERIAL
Local, systemic, and other AEs
References
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Associated Data
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Supplementary Materials
Local, systemic, and other AEs