Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination
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Abstract
Abstract The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. The Dominican Republic was among the first countries in recommending the administration of a third dose COVID-19 vaccine to address potential waning immunity and reduced effectiveness against variants. Here, we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants that had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that heterologous CoronaVac prime followed by BNT162b2 booster regimen induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and Delta variant, resembling the titers obtained after two doses of mRNA vaccines. While neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine, BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared to two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 6.3-fold and 2.7-fold for Omicron compared to ancestral and Delta variant, respectively. Surprisingly, previous SARS-CoV-2 infection did not affect the neutralizing titers for Omicron in participants that received the heterologous regimen. Our findings have immediate implications for multiples countries that previously used a two-dose regimen of CoronaVac and reinforce the notion that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.
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In multiple trials, neutralizing antibody titers after the second dose of mRNA-based vaccines were highly reduced for omicron compared with delta and especially compared with the wild-type variant, while the third dose significantly improved antibody neutralization titers.
“In all cases, neutralizing antibody titers after the second dose of mRNA-based vaccines were highly reduced for omicron (B.1.1.529) compared with delta (B.1.617.2) and especially compared with the wild-type variant, while the third dose significantly improved antibody neutralization titers.110,112,113”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [112]
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- Authors
- Pérez-Then, E., Lucas, C., Monteiro, V. S., Miric, M., Brache, V., Cochon, L., Vogels, C. B. F., Malik, A. A., De la Cruz, E., Jorge, A., De los Santos, M., Leon, P., Breban, M. I., Billig, K., Yildirim, I., Pearson, C., Downing, R., Gagnon, E., Muyombwe, A., Razeq, J., Campbell, M., Ko, A. I., Omer, S. B., Grubaugh, N. D., Vermund, S. H., & Iwasaki, A.
- Affiliations
- Yale University (US)
- Profamilia (DO)
- Connecticut Department of Public Health (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lucas, Carolina
- Iwasaki, Akiko
- ORCID
- Venue
- Nature Medicine
- Published
- 2022-01-20
- Volume
- 28
- Issue
- 3
- Pages
- 481-485
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC8938264
- OpenAlex
- W4206675538
- Cited by
- 401
- References
- 20
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 47 · 2023: 114 · 2022: 207 · 2021: 1
- FWCI
- 47.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Medicine (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (N/A)
- Pew Charitable Trusts (N/A)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- Omicron variant, Delta variant, neutralizing antibodies, CoronaVac, BNT162b2 mRNA vaccine, inactivated vaccine, spike protein mutations, immune evasion, humoral immunity, booster vaccination
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, BNT162 Vaccine, Antibodies, Viral, Humans, Vaccination, Vaccines, Synthetic, Antibodies, Neutralizing
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