. 2023 Apr 18;4(4):101018.

doi: 10.1016/j.xcrm.2023.101018. Epub 2023 Mar 27.

Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques

Jingyou Yu¹, Paul V Thomas², Michaela Sciacca¹, Cindy Wu¹, Jinyan Liu¹, Xuan He¹, Jessica Miller¹, Nicole P Hachmann¹, Nehalee Surve¹, Katherine McMahan¹, Catherine Jacob-Dolan³, Olivia Powers¹, Kevin Hall¹, Julia Barrett¹, David Hope¹, Camille R Mazurek¹, Tetyana Murdza¹, William C Chang⁴, Emily Golub², Phyllis A Rees², Caroline E Peterson², Agnes Hajduczki², Wei-Hung Chen², Elizabeth J Martinez², Elizabeth Hussin², Camille Lange², Hua Gong⁵, Gary R Matyas⁵, Mangala Rao⁵, Mehul Suthar⁶, Mona Boursiquot⁷, Anthony Cook⁷, Laurent Pessaint⁷, Mark G Lewis⁷, Hanne Andersen⁷, Diane L Bolton⁸, Nelson L Michael⁹, M Gordon Joyce¹⁰, Kayvon Modjarrad⁴, Dan H Barouch¹¹

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
² Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
⁴ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA.
⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁶ Emory University, Atlanta, GA, USA.
⁷ Bioqual, Rockville, MD, USA.
⁸ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁹ Center for Infectious Diseases Research, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA.
¹⁰ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: gjoyce@eidresearch.org.
¹¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: dbarouch@bidmc.harvard.edu.

PMID: 37023746
PMCID: PMC10040355
DOI: 10.1016/j.xcrm.2023.101018

Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques

Jingyou Yu et al. Cell Rep Med. 2023.

. 2023 Apr 18;4(4):101018.

doi: 10.1016/j.xcrm.2023.101018. Epub 2023 Mar 27.

Authors

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
² Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
⁴ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA.
⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁶ Emory University, Atlanta, GA, USA.
⁷ Bioqual, Rockville, MD, USA.
⁸ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁹ Center for Infectious Diseases Research, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA.
¹⁰ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: gjoyce@eidresearch.org.
¹¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: dbarouch@bidmc.harvard.edu.

PMID: 37023746
PMCID: PMC10040355
DOI: 10.1016/j.xcrm.2023.101018

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines demonstrate reduced protection against acquisition of BA.5 subvariant but are still effective against severe disease. However, immune correlates of protection against BA.5 remain unknown. We report the immunogenicity and protective efficacy of vaccine regimens consisting of the vector-based Ad26.COV2.S vaccine and the adjuvanted spike ferritin nanoparticle (SpFN) vaccine against a high-dose, mismatched Omicron BA.5 challenge in macaques. The SpFNx3 and Ad26 + SpFNx2 regimens elicit higher antibody responses than Ad26x3, whereas the Ad26 + SpFNx2 and Ad26x3 regimens induce higher CD8 T cell responses than SpFNx3. The Ad26 + SpFNx2 regimen elicits the highest CD4 T cell responses. All three regimens suppress peak and day 4 viral loads in the respiratory tract, which correlate with both humoral and cellular immune responses. This study demonstrates that both homologous and heterologous regimens involving Ad26.COV2.S and SpFN vaccines provide robust protection against a mismatched BA.5 challenge in macaques.

Keywords: B cell; BA.5; Omicron; SARS-CoV-2; T cell; antibody; macaque; vaccine.

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Conflict of interest statement

Declaration of interests D.H.B. is a co-inventor on provisional vaccine patents licensed to Janssen (63/121,482; 63/133,969; 63/135,182) and serves as a consultant to Pfizer. M.G.J. and K.M. are co-inventors on international patent application WO/2021/178971 A1 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” M.G.J. is a co-inventor on international patent application WO/2018/081318 and a US patent 10,960,070 entitled “Pre-fusion coronavirus spike proteins and their use.” K.M.’s current affiliation is Pfizer.

Figures

**Figure 1**
Study schema Vaccine groups and timing of immunization and challenge are shown.

**Figure 2**
Humoral immune responses following vaccination Antibody responses at weeks 0 (baseline), 10 (post-first boost), 32 (at second boost), and 34 (post-second boost) following vaccination with SpFNx3, Ad26 + SpFNx2, Ad26x3, or sham (N = 24; n = 6/group). (A) Neutralizing antibody (NAb) titers (NT50) by a luciferase-based pseudovirus neutralization assay. Dotted lines represent limits of quantitation. Medians (red bars) are shown. BA.5-specific NAbs in the vaccinated groups were compared with sham control group by two-sided Mann-Whitney tests. Only statistically significant differences ∗p < 0.05 and ∗∗p < 0.01 are presented. (B) Receptor-binding domain (RBD)-specific endpoint 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; purple), and BA.1 (green) variants and BA.5 (bright red). All values are plotted on a logarithmic scale. Dotted lines represent limits of quantitation. Red bars represent medians of 6 biological replicates.

**Figure 3**
Cellular immune responses following vaccination (A and B) T cell responses at week 4 (post-prime), 10 (post-first boost), and 34 (post-second boost) following vaccination with SpFNx3, Ad26 + SpFNx2, Ad26x3, or sham (N = 24; n = 6/group). Pooled peptide spike-specific IFN-γ (A) CD4⁺ T cell responses and (B) CD8⁺ 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), B.1.351 (Beta; purple), and BA.5 (bright red) variants. All values are plotted on a logarithmic scale. Dotted lines represent limits of quantitation. Red bars represent medians of 6 biological replicates.

**Figure 4**
Viral loads following SARS-CoV-2 Omicron BA.5 challenge (A) Log subgenomic RNA (sgRNA) copies/mL in bronchoalveolar lavage (BAL) following SARS-CoV-2 Omicron BA.5 challenge. (B) Log sgRNA copies/swab in nasal swabs (NSs) following SARS-CoV-2 Omicron challenge. Medians (red lines) are shown. The peak and day 4 viral loads were compared. (C) Log sgRNA copies/mL in BAL at peak and on day 4 following SARS-CoV-2 BA.5 Omicron challenge. (D) Log sgRNA copies/swab in NSs at peak and on day 4 following SARS-CoV-2 Omicron BA.5 challenge. Viral load values are plotted on a logarithmic scale. 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 < 0.01.

**Figure 5**
Immune correlates of protection analyses (A and B) Correlations of week 34 NAb titers, CD8⁺ and CD4⁺ T cell responses, and memory B cell responses with peak sgRNA copies/mL in BAL (A) and peak sgRNA copies/swab in NSs (B) are shown. All values are plotted on a logarithmic scale. Correlations were assessed by two-sided Spearman rank-correlation tests. R and p values and a regression line of best fit are shown.

**Figure 6**
Additional immune correlates analyses (A) Correlations of week 34 CD8 T cell responses with NAb, CD4 T cell responses, and memory B cell responses. (B) Correlations of week 34 NAb titers, CD4⁺ T cell responses, and memory B cell responses are shown. All values are plotted on a logarithmic scale. Correlations were assessed by two-sided Spearman rank-correlation tests. R and p values and a regression line of best fit are shown.

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References

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Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques

Affiliations

Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

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