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Vaccine Protection Against the SARS-CoV-2 Omicron Variant in Macaques
Abishek Chandrashekar1, Jingyou Yu1, Katherine McMahan1
1Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Background:
The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. Immune correlates of vaccine protection against Omicron are not known.
Methods:
30 cynomolgus macaques were immunized with homologous and heterologous prime-boost regimens with the mRNA-based BNT162b2 vaccine and the adenovirus vector-based Ad26.COV2.S vaccine. Following vaccination, animals were challenged with the SARS-CoV-2 Omicron variant by the intranasal and intratracheal routes.
Results:
Omicron neutralizing antibodies were observed following the boost immunization and were higher in animals that received BNT162b2, whereas Omicron CD8+ T cell responses were higher in animals that received Ad26.COV2.S. Following Omicron challenge, sham controls showed more prolonged virus in nasal swabs than in bronchoalveolar lavage. Vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs, showing that current vaccines provide substantial protection against Omicron in this model. However, vaccinated animals that had moderate levels of Omicron neutralizing antibodies but negligible Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Virologic control correlated with both antibody and T cell responses.
Conclusions:
BNT162b2 and Ad26.COV2.S provided robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in macaques. Protection against this highly mutated SARS-CoV-2 variant correlated with both humoral and cellular immune responses.
Insights
Current vaccines offer substantial protection against the SARS-CoV-2 Omicron variant. Both antibody and T cell responses are crucial for controlling the virus, especially in the upper respiratory tract.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- The emergence of the SARS-CoV-2 Omicron variant raised concerns about vaccine efficacy in highly vaccinated populations.
- Immune correlates of protection against Omicron remain largely unknown.
Approach:
- Cynomolgus macaques received homologous or heterologous prime-boost regimens with BNT162b2 (mRNA) or Ad26.COV2.S (adenovirus vector) vaccines.
- Vaccinated macaques were subsequently challenged with the SARS-CoV-2 Omicron variant via intranasal and intratracheal routes.
Key Points:
- Both BNT162b2 and Ad26.COV2.S vaccines induced Omicron-specific neutralizing antibodies and T cell responses.
- Vaccinated macaques showed rapid control of viral load in the lower respiratory tract and, largely, in the upper respiratory tract.
- Effective virologic control correlated with the presence of both neutralizing antibodies and CD8+ T cell responses.
Conclusions:
- BNT162b2 and Ad26.COV2.S vaccines confer robust protection against high-dose Omicron variant challenge in a macaque model.
- Humoral and cellular immune responses are essential for comprehensive protection against the highly mutated Omicron variant.
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