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[Preprint]. 2022 Feb 7:2022.02.06.479285.
doi: 10.1101/2022.02.06.479285.

Vaccine Protection Against the SARS-CoV-2 Omicron Variant in Macaques

Abishek Chandrashekar  1 , Jingyou Yu  1 , Katherine McMahan  1 , Catherine Jacob-Dolan  1   2 , Jinyan Liu  1 , Xuan He  1 , David Hope  1 , Tochi Anioke  1 , Julia Barrett  1 , Benjamin Chung  1 , Nicole P Hachmann  1 , Michelle Lifton  1 , Jessica Miller  1 , Olivia Powers  1 , Michaela Sciacca  1 , Daniel Sellers  1 , Mazuba Siamatu  1 , Nehalee Surve  1 , Haley VanWyk  1 , Huahua Wan  1 , Cindy Wu  1 , Laurent Pessaint  3 , Daniel Valentin  3 , Alex Van Ry  3 , Jeanne Muench  3 , Mona Boursiquot  3 , Anthony Cook  3 , Jason Velasco  3 , Elyse Teow  3 , Adrianus C M Boon  4 , Mehul S Suthar  5 , Neharika Jain  6 , Amanda J Martinot  6 , Mark G Lewis  3 , Hanne Andersen  3 , Dan H Barouch  1   2
Affiliations

Vaccine Protection Against the SARS-CoV-2 Omicron Variant in Macaques

Abishek Chandrashekar et al. bioRxiv. .

Update in

  • Vaccine protection against the SARS-CoV-2 Omicron variant in macaques.
    Chandrashekar A, Yu J, McMahan K, Jacob-Dolan C, Liu J, He X, Hope D, Anioke T, Barrett J, Chung B, Hachmann NP, Lifton M, Miller J, Powers O, Sciacca M, Sellers D, Siamatu M, Surve N, VanWyk H, Wan H, Wu C, Pessaint L, Valentin D, Van Ry A, Muench J, Boursiquot M, Cook A, Velasco J, Teow E, Boon ACM, Suthar MS, Jain N, Martinot AJ, Lewis MG, Andersen H, Barouch DH. Chandrashekar A, et al. Cell. 2022 Apr 28;185(9):1549-1555.e11. doi: 10.1016/j.cell.2022.03.024. Epub 2022 Mar 17. Cell. 2022. PMID: 35427477 Free PMC article.

Abstract

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.

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Conflict of interest statement

Competing Interests

DHB is a co-inventor on provisional vaccine patents (63/121,482; 63/133,969; 63/135,182). The authors report no other conflict of interest. ACMB has received funding from Abbvie for the commercial development of SARS-CoV-2 mAbs.

Figures

Figure 1.
Figure 1.. Humoral immune responses following vaccination.
Antibody responses at weeks 0 (baseline), 8 (post-prime), 14 (pre-boost), and 18 (post-boost) following vaccination with BNTx3, BNTx2/Ad26, Ad26/BNT, Ad26×2, or sham (N=30; N=6/group). A, Neutralizing antibody (NAb) titers by a luciferase-based pseudovirus neutralization assay. B, Receptor binding domain (RBD)-specific binding antibody titers by ELISA. Responses were measured against the SARS-CoV-2 WA1/2020 (black), B.1.617.2 (Delta; blue), B.1.351 (Beta; red), and B.1.1.529 (Omicron; green) variants. Dotted lines represent limits of quantitation. Medians (red bars) are shown.
Figure 1.
Figure 1.. Humoral immune responses following vaccination.
Antibody responses at weeks 0 (baseline), 8 (post-prime), 14 (pre-boost), and 18 (post-boost) following vaccination with BNTx3, BNTx2/Ad26, Ad26/BNT, Ad26×2, or sham (N=30; N=6/group). A, Neutralizing antibody (NAb) titers by a luciferase-based pseudovirus neutralization assay. B, Receptor binding domain (RBD)-specific binding antibody titers by ELISA. Responses were measured against the SARS-CoV-2 WA1/2020 (black), B.1.617.2 (Delta; blue), B.1.351 (Beta; red), and B.1.1.529 (Omicron; green) variants. Dotted lines represent limits of quantitation. Medians (red bars) are shown.
Figure 2.
Figure 2.. Cellular immune responses following vaccination.
T cell responses at weeks 14 (pre-boost) and 18 (post-boost) following vaccination with BNTx3, BNTx2/Ad26, Ad26/BNT, Ad26×2, or sham (N=30; N=6/group). Pooled peptide Spike-specific IFN-γ (A) CD8+ T cell responses and (B) CD4+ T cell responses by intracellular cytokine staining assays. Responses were measured against the SARS-CoV-2 WA1/2020 (black), B.1.617.2 (Delta; blue), and B.1.1.529 (Omicron; green) variants. Dotted lines represent limits of quantitation. Medians (red bars) are shown.
Figure 2.
Figure 2.. Cellular immune responses following vaccination.
T cell responses at weeks 14 (pre-boost) and 18 (post-boost) following vaccination with BNTx3, BNTx2/Ad26, Ad26/BNT, Ad26×2, or sham (N=30; N=6/group). Pooled peptide Spike-specific IFN-γ (A) CD8+ T cell responses and (B) CD4+ T cell responses by intracellular cytokine staining assays. Responses were measured against the SARS-CoV-2 WA1/2020 (black), B.1.617.2 (Delta; blue), and B.1.1.529 (Omicron; green) variants. Dotted lines represent limits of quantitation. Medians (red bars) are shown.
Figure 3.
Figure 3.. Viral loads following SARS-CoV-2 Omicron challenge.
A, Log subgenomic RNA (sgRNA) copies/ml in bronchoalveolar lavage (BAL) following SARS-CoV-2 Omicron challenge. B, Log subgenomic RNA (sgRNA) copies/swab in nasal swabs (NS) following SARS-CoV-2 Omicron challenge. Medians (red lines) are shown.
Figure 3.
Figure 3.. Viral loads following SARS-CoV-2 Omicron challenge.
A, Log subgenomic RNA (sgRNA) copies/ml in bronchoalveolar lavage (BAL) following SARS-CoV-2 Omicron challenge. B, Log subgenomic RNA (sgRNA) copies/swab in nasal swabs (NS) following SARS-CoV-2 Omicron challenge. Medians (red lines) are shown.
Figure 4.
Figure 4.. Comparison of peak and day 4 viral loads.
A, Log subgenomic RNA (sgRNA) copies/ml in bronchoalveolar lavage (BAL) at peak and on day 4 following SARS-CoV-2 Omicron challenge. B, Log subgenomic RNA (sgRNA) copies/swab in nasal swabs (NS) at peak and on day 4 following SARS-CoV-2 Omicron challenge. Dotted lines represent limits of quantitation. Medians (red bars) are shown. Vaccinated groups were compared with the sham controls by two-sided Mann-Whitney tests. *, P<0.05.
Figure 4.
Figure 4.. Comparison of peak and day 4 viral loads.
A, Log subgenomic RNA (sgRNA) copies/ml in bronchoalveolar lavage (BAL) at peak and on day 4 following SARS-CoV-2 Omicron challenge. B, Log subgenomic RNA (sgRNA) copies/swab in nasal swabs (NS) at peak and on day 4 following SARS-CoV-2 Omicron challenge. Dotted lines represent limits of quantitation. Medians (red bars) are shown. Vaccinated groups were compared with the sham controls by two-sided Mann-Whitney tests. *, P<0.05.
Figure 5.
Figure 5.. Immunologic space defined by Omicron NAb titer and Omicron CD8+ T cell responses.
Plot of all 30 animals by their post-boost Omicron NAb titer and Omicron CD8+ T cell responses. Red dots represent the 10 animals that failed to control virus by day 7 in NS (6 controls, 4 vaccinated animals). The dotted line represents the region of immunologic space, defined post-hoc, which was associated with failure of virologic control. Red arrows show representative animals with low NAb titers but high CD8+ T cell responses, or high NAb titers but low CD8+ cell responses, which showed rapid virologic control.
See this image and copyright information in PMC

References

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