Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Corbett, Kizzmekia S.; Nason, Martha; Flach, Britta; Gagné, Matthew; O’Connell, Sarah; Johnston, Timothy S.; Shah, Shruti; Edara, Venkata Viswanadh; Floyd, Katharine; Lai, Lilin; McDanal, Charlene; Francica, Joseph R.; Flynn, Barbara J.; Wu, Kai; Choi, Angela; Koch, Matthew; Abiona, Olubukola M.; Werner, Anne P.; Moliva, Juan I.; Andrew, Shayne F.; Donaldson, Mitzi M.; Fintzi, Jonathan; Flebbe, Dillon R.; Lamb, Evan; Noe, Amy T.; Nurmukhambetova, Saule; Provost, Samantha J.; Cook, Anthony; Dodson, Alan; Faudree, Andrew; Greenhouse, Jack; Kar, Swagata; Pessaint, Laurent; Porto, Maciel; Steingrebe, Katelyn; Valentin, Daniel; Zouantcha, Serge; Bock, Kevin W.; Minai, Mahnaz; Nagata, Bianca M.; Wetering, Renee van de; Boyoglu-Barnum, Seyhan; Leung, Kwanyee; Shi, Wei; Yang, Eun Sung; Zhang, Yi; Todd, John Paul; Wang, Lingshu; Alvarado, Gabriela; Andersen, Hanné; Foulds, Kathryn E.; Edwards, Darin K.; Mascola, John R.; Moore, Ian N.; Lewis, Mark G.; Carfı́, Andrea; Montefiori, David C.; Suthar, Mehul S.; McDermott, Adrian B.; Roederer, Mario; Sullivan, Nancy J.; Douek, Daniel C.; Graham, Barney S.; Seder, Robert A.

doi:10.1126/science.abj0299

Cited by 278 publications

(252 citation statements)

References 49 publications

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“…A remarkable finding of mRNA vaccines immunogenicity studies is that levels of anti-RBD and neutralizing antibodies titers do not change after the 2nd dose in individuals previously infected, suggesting that the 2nd dose of BNT122b2 or other vaccines may not be necessary in previously infected immunocompetent individuals [30][31][32]. In our study, we tested vaccinated HCWs by anti-N and anti-RBD 1-2 weeks after the 2nd dose.…”

Section: Discussionmentioning

confidence: 86%

“…The present analysis assumes according to findings from previous reports that NA and anti-RBD are correlates of protection against SARS-CoV-2 [5,[21][22][23][24][25][26]31]. Although the mechanism of protection is complex including several aspects of humoral and cell-mediated immunity, the role of neutralizing antibodies seems profound.…”

Section: Discussionmentioning

confidence: 94%

“…In a recent study including non-human primates, purified spike antibodies elicited by mRNA-1273 vaccine were associated with a dose-dependent protection in a highly pathogenic hamster model [31].…”

Section: Discussionmentioning

confidence: 99%

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Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

et al. 2021

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BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 94%

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Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

et al. 2021

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“…Abs that bind to specific sites on the RBD (15)(16)(17)(18)(19)(20)(21)(22), the NTD (23)(24)(25)(26), or the fusion machinery stem helix (27)(28)(29)(30)(31) interfere with receptor attachment or membrane fusion. Serum neutralizing Ab titers are a correlate of protection against SARS-CoV-2 in non-human primates (32)(33)(34)(35).…”

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confidence: 99%

Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants

McCallum

Walls

Sprouse

et al. 2021

Preprint

110

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Worldwide SARS-CoV-2 transmission leads to the recurrent emergence of variants, such as the recently described B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.2+ (delta+). The B.1.617.2 (delta) variant of concern is causing a new wave of infections in many countries, mostly affecting unvaccinated individuals, and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing the impact of individual mutations on immune evasion. Mutations in the B.1.617.1 (kappa) and B.1.617.2 (delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including an unexpected remodeling of the B.1.617.2 (delta) N-terminal domain. The binding affinity of the B.1.617.1 (kappa) and B.1.617.2 (delta) receptor-binding domain for ACE2 is comparable to the ancestral virus whereas B.1.617.2+ (delta+) exhibits markedly reduced affinity. We describe a previously uncharacterized class of N-terminal domain-directed human neutralizing monoclonal antibodies cross-reacting with several variants of concern, revealing a possible target for vaccine development.

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“…Furthermore, an international standard for SARS-CoV-2 antibodies (NIBSC 20/136) was issued by the WHO to improve the comparability of such assays 11 . Although there is currently no general recommendation to determine antibody levels in all individuals after SARS-CoV-2 vaccination, this is reasonable from a scientific perspective in the search for a correlate of protection and has been done in numerous studies 12–19 . Moreover, it is now known that suboptimal or even lack of response to vaccination can occur in specific groups like immunocompromised patients 20–26 .…”

Section: Introductionmentioning

confidence: 99%

The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

Perkmann¹,

Mucher²,

Perkmann-Nagele³

et al. 2021

Preprint

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Objectives Various commercial anti-Spike SARS-CoV-2 antibody tests are used for studies and in clinical settings after vaccination. An international standard for SARS-CoV-2 antibodies has been established to achieve comparability of such tests, allowing conversions to BAU/ml. This study aimed to investigate the comparability of antibody tests regarding the timing of blood collection after vaccination. Methods For this prospective observational study, antibody levels of 50 participants with homologous AZD1222 vaccination were evaluated at 3 and 11 weeks after the first dose and 3 weeks after the second dose using two commercial anti-Spike binding antibody assays (Roche and Abbott) and a surrogate neutralization assay (sVNT). Results The correlation between Roche and Abbott changed significantly depending on the time point studied. Although 3 weeks after the first dose, Abbott provided values three times higher than Roche, 11 weeks after the first dose, the values for Roche were twice as high as for Abbott, and 3 weeks after the second dose even 5-6 times higher. Conclusions The comparability of quantitative anti-Spike SARS-CoV-2 antibody tests is highly dependent on the timing of blood collection after vaccination. Therefore, standardization of the timing of blood collection might be necessary for the comparability of different quantitative SARS-COV-2 antibody assays.

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Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Cited by 278 publications

References 49 publications

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants

The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

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