Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19
Authors: Wey Wen Lim, Loretta Mak, Gabriel M Leung, Benjamin J Cowling, Malik Peiris
Journal: The Lancet Microbe (2021)

We report here comparative data on SARS-CoV-2 vaccine immunogenicity in health-care workers in Hong Kong who received either the BNT162b2 vaccine (Comirnaty; Fosun–BioNTech) or the inactivated virus (vero cell) vaccine (Coronavac; Sinovac). We collected blood samples before vaccination, before the second dose, and 21–35 days after the second dose. We tested the samples for antibodies to SARS-CoV-2 using an ELISA to detect antibodies that bind to the receptor binding domain of the spike protein, testing ELISA-positive samples for neutralising antibodies with a surrogate virus neutralisation (sVNT) assay, and then a plaque reduction neutralisation test (PRNT) with live SARS-CoV-2 virus.1Perera RA Mok CK Tsang OT et al.Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020.Euro Surveill. 2020; 252000421Crossref Scopus (238) Google Scholar, 2Perera RAPM Ko R Tsang OTY et al.Evaluation of a SARS-CoV-2 surrogate virus neutralization test for detection of antibody in human, canine, cat, and hamster sera.J Clin Microbiol. 2021; 59: e02504-e02520Crossref PubMed Scopus (83) Google Scholar We enrolled a cohort of 1442 health-care workers from public and private hospitals and medical clinics in Hong Kong and arranged for longitudinal collection of blood samples after obtaining informed consent. Here we present our preliminary laboratory testing results on 93 participants for whom we have complete data on antibody concentrations before vaccination, after the first dose, and after the second dose. These included 63 participants (55·6% male, median age 37 years, range 26–60 years) who were fully vaccinated with the BNT162b2 vaccine and 30 participants (23·3% male, median age 47 years, range 31–65 years) who received both doses of the inactivated vaccine. In health-care workers who received the BNT162b2 vaccine, antibody concentrations measured by ELISA and sVNT rose substantially after the first dose and then rose again after the second dose of vaccination (appendix). In a subset of 12 participants for whom we also had PRNT results, after the second dose the geometric mean PRNT50 titre was 269 and the geometric mean PRNT90 titre was 113. In contrast, the health-care workers who received the inactivated vaccine had low antibody concentrations by ELISA and sVNT after the first dose, rising to moderate concentrations after the second dose. In a subset of 12 participants, after the second dose, the geometric mean PRNT50 titre was 27 and the geometric mean PRNT90 titre was 8·4. Neutralising antibody titres have been proposed as a correlate of protection for SARS-CoV-2 vaccines.3Khoury DS Cromer D Reynaldi A et al.Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.Nat Med. 2021; (published online May 17.)https://doi.org/10.1038/s41591-021-01377-8Crossref PubMed Scopus (2126) Google Scholar, 4Koch T Mellinghoff SC Shamsrizi P Addo MM Dahlke C Correlates of vaccine-induced protection against SARS-CoV-2.Vaccines (Basel). 2021; 9: 238Crossref PubMed Scopus (37) Google Scholar, 5Earle KA Ambrosino DM Fiore-Gartland A et al.Evidence for antibody as a protective correlate for COVID-19 vaccines.Vaccine. 2021; 39: 4423-4428Crossref PubMed Scopus (488) Google Scholar The difference in concentrations of neutralising antibodies identified in our study could translate into substantial differences in vaccine effectiveness. Our study did not include data on other potential correlates of protection such as T cells or antibody-dependent cellular cytotoxicity antibody. Future studies could investigate alternative strategies to increase antibody concentrations and clinical protection in recipients of inactivated vaccines, including administration of booster doses. This work was supported by the Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong. BJC is supported by the AIR@innoHK programme of the Innovation and Technology Commission of the Government of Hong Kong. BJC reports honoraria from Sanofi Pasteur, GlaxoSmithKlein, Moderna, and Roche. All other authors report no other potential competing interests. Download .pdf (.11 MB) Help with pdf files Supplementary appendix Correction to Lancet Microbe 2021; published online June 15. https://doi.org/10.1016/S2666-5247(21)00177-4Lim WW, Mak L, Leung GM, Cowling BJ, Peiris M. Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19. Lancet Microbe 2021; published online June 15. https://doi.org/10.1016/S2666-5247(21)00177-4—In this Correspondence, the declaration of interests should have included the grant number (COVID190119) for the Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong. This correction has been made as of Aug 4, 2021. Full-Text PDF Open Access