Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.
Sankhala, R.S., Lal, K.G., Jensen, J.L., Dussupt, V., Mendez-Rivera, L., Bai, H., Wieczorek, L., Mayer, S.V., Zemil, M., Wagner, D.A., Townsley, S.M., Hajduczki, A., Chang, W.C., Chen, W.H., Donofrio, G.C., Jian, N., King, H.A.D., Lorang, C.G., Martinez, E.J., Rees, P.A., Peterson, C.E., Schmidt, F., Hart, T.J., Duso, D.K., Kummer, L.W., Casey, S.P., Williams, J.K., Kannan, S., Slike, B.M., Smith, L., Swafford, I., Thomas, P.V., Tran, U., Currier, J.R., Bolton, D.L., Davidson, E., Doranz, B.J., Hatziioannou, T., Bieniasz, P.D., Paquin-Proulx, D., Reiley, W.W., Rolland, M., Sullivan, N.J., Vasan, S., Collins, N.D., Modjarrad, K., Gromowski, G.D., Polonis, V.R., Michael, N.L., Krebs, S.J., Joyce, M.G.(2024) Nat Commun 15: 200-200
- PubMed: 38172512
- DOI: https://doi.org/10.1038/s41467-023-44265-0
- Primary Citation of Related Structures:
8FHY, 8FI9 - PubMed Abstract:
The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.
Organizational Affiliation:
Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.