key: cord-0786020-fchb5e10 authors: Cowling, B. J.; Wong, I. O. L.; Shiu, E. Y. C.; Lai, A. Y. T.; Cheng, S. M. S.; Chaothai, S.; Kwan, K. K. H.; Martin-Sanchez, M.; Poon, L. L. M.; Ip, D. K. M.; Leung, G. M.; Leung, N. H. L.; Peiris, M. title: Strength and durability of antibody responses to BNT162b2 and CoronaVac date: 2022-02-15 journal: nan DOI: 10.1101/2022.02.11.22270848 sha: 8f6f8e55d7f550476fc05feb2decc034ee8edb6b doc_id: 786020 cord_uid: fchb5e10 We studied 2864 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine (Comirnaty, BioNTech/Fosun Pharma). We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women. Vaccines for coronavirus disease 2019 (COVID-19) provide protection against infection and 33 can also ameliorate disease severity if breakthrough infections occur [1] . February 2022, 11.7 million vaccine doses have been administered, with 74% of the 46 population of about 7.4 million residents receiving at least one vaccine dose, 67% receiving 47 at least two doses, and 16% receiving three doses. Of the 11.7 million doses administered to 48 date, 4.5 million were CoronaVac and 7.2 million were BNT162b2. Here, we followed up 49 vaccinated individuals in Hong Kong to study the strength and durability of antibody 50 responses to vaccination for up to six months after the second dose. 51 which was initially designed to study influenza and later also expanded to COVID-19, we 57 enrolled individuals from the community starting in July 2020, and included individuals 58 regardless of COVID-19 vaccination status. For analyses reported here we include the subset 59 of study participants who were aged ≥18y and have received two doses of COVID-19 60 vaccination. Blood is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint We assessed mean antibody levels measured by ELISA (optical density, OD) and sVNT (% 112 inhibition) after the first and second dose of COVID-19 vaccination. It was recommended 113 that individuals should receive their second dose 21 and 28 days after the first dose for 114 BNT162b2 and CoronaVac, respectively. We did not include any samples collected after 115 receipt of a third dose, or any samples collected after a confirmed SARS-CoV-2 infection. 116 Differences in antibody levels between vaccine type overall or within each category of age or 117 sex were compared using t-tests. To evaluate the duration after which antibody level fall 118 below the manufacturer's defined sVNT threshold of seropositivity at 30% inhibition 119 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 15, 2022. ; https://doi.org/10.1101/2022.02.11.22270848 doi: medRxiv preprint 44.7% male). Additional information on the demographics of study participants is provided 131 in Appendix Table 1 . 132 133 Antibody levels increased to moderate levels following two doses of CoronaVac ( Figure 1A ) 134 compared to very high levels following two doses of BNT162b2 ( Figure 1B) . The mean 135 sVNT antibody levels measured against ancestral virus at 14-42 days after the second dose 136 for CoronaVac were 53.7% (95% confidence interval, CI: 51.2, 56.3) and for BNT162b2 137 were 94.3% (95% CI: 93.8, 94.7), with significant differences between the two vaccines 138 overall and within each age group (Appendix Table 2 ). For both vaccines, the observed post-139 vaccination levels had a slight inverse correlation with age, and average levels were slightly 140 higher in females than in males (p-values <0.01 for these within-group comparisons) 141 (Appendix Table 2 ). Overall, antibody levels remained below the threshold of 30% after the 142 second dose in 23% and 0.5% of participants who received CoronaVac and BNT162b2, 143 respectively. In particular, the antibody levels did not reach the threshold of 30% in 51% of 144 older adults ≥60 years old who received CoronaVac vaccination. 145 146 Antibody levels started to decline gradually over time starting from one month after recipient 147 of the second dose for both vaccines, with faster antibody waning in the recipients of 148 CoronaVac ( Figure 1C and 1D ). In recipients of CoronaVac, the fitted curve for average 149 antibody level fell below the threshold of 30% by around 4 months after second dose, while 150 remaining elevated for at least six months in recipients of BNT162b2. Consistently, we 151 continued to observe significant differences in antibody levels 4-6 months after vaccination 152 between the two vaccines overall and within each age group (Appendix Table 3 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 15, 2022. ; https://doi.org/10.1101/2022.02.11.22270848 doi: medRxiv preprint Specifically, sVNT antibody levels fell to below the threshold of 30% in 84% of participants 156 who received CoronaVac, versus none among those who received BNT162b2. However, with 157 a smaller sample size here we were not able to identify statistically significant differences by 158 age or sex within each vaccine group. We also examined antibody levels by ELISA, finding 159 similar comparative patterns of boosting and waning between the two vaccine types 160 (Appendix Figure 1) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 15, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 15, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 15, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 15, 2022. ; https://doi.org/10.1101/2022.02.11.22270848 doi: medRxiv preprint Challenges in ensuring global access to 222 COVID-19 vaccines: production, affordability, allocation, and deployment Neutralizing antibody levels are highly 225 predictive of immune protection from symptomatic SARS-CoV-2 infection Correlates of protection against symptomatic and 228 asymptomatic SARS-CoV-2 infection Evidence for antibody as a protective 230 correlate for COVID-19 vaccines Comparative immunogenicity of 232 mRNA and inactivated vaccines against COVID-19 BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong 14-42 days after the receipt of the second vaccine dose of an inactivated (CoronaVac) or 308 mRNA (BNT162b2) vaccine, overall and by age and sex (n=1431