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Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

ABSTRACT: Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)^1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID₅₀) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

SUBMITTER: Saunders KO

PROVIDER: S-EPMC8528238 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Saunders Kevin O KO Lee Esther E Parks Robert R Martinez David R DR Li Dapeng D Chen Haiyan H Edwards Robert J RJ Gobeil Sophie S Barr Maggie M Mansouri Katayoun K Alam S Munir SM Sutherland Laura L LL Cai Fangping F Sanzone Aja M AM Berry Madison M Manne Kartik K Bock Kevin W KW Minai Mahnaz M Nagata Bianca M BM Kapingidza Anyway B AB Azoitei Mihai M Tse Longping V LV Scobey Trevor D TD Spreng Rachel L RL Rountree R Wes RW DeMarco C Todd CT Denny Thomas N TN Woods Christopher W CW Petzold Elizabeth W EW Tang Juanjie J Oguin Thomas H TH Sempowski Gregory D GD Gagne Matthew M Douek Daniel C DC Tomai Mark A MA Fox Christopher B CB Seder Robert R Wiehe Kevin K Weissman Drew D Pardi Norbert N Golding Hana H Khurana Surender S Acharya Priyamvada P Andersen Hanne H Lewis Mark G MG Moore Ian N IN Montefiori David C DC Baric Ralph S RS Haynes Barton F BF

Nature 20210510 7864

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)<sup>1-4</sup>. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted w ...[more]

PMID: 33971664

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Project description:The first exposure to influenza is presumed to shape the B-cell antibody repertoire, leading to preferential enhancement of the initially formed responses during subsequent exposure to viral variants. Here, we investigated whether this principle remains applicable when there are large genetic and antigenic differences between primary and secondary influenza virus antigens. Because humans usually have a complex history of influenza virus exposure, we conducted this investigation in influenza-naive cynomolgus macaques. Two groups of six macaques were immunized four times with influenza virus-like particles (VLPs) displaying either one (monovalent) or five (pentavalent) different hemagglutinin (HA) antigens derived from seasonal H1N1 (H1N1) strains. Four weeks after the final immunization, animals were challenged with pandemic H1N1 (H1N1pdm09). Although immunization resulted in robust virus-neutralizing responses to all VLP-based vaccine strains, there were no cross-neutralization responses to H1N1pdm09, and all animals became infected. No reductions in viral load in the nose or throat were detected in either vaccine group. After infection, strong virus-neutralizing responses to H1N1pdm09 were induced. However, there were no increases in virus-neutralizing titers against four of the five H1N1 vaccine strains; and only a mild increase was observed in virus-neutralizing titer against the influenza A/Texas/36/91 vaccine strain. After H1N1pdm09 infection, both vaccine groups showed higher virus-neutralizing titers against two H1N1 strains of intermediate antigenic distance between the H1N1 vaccine strains and H1N1pdm09, compared with the naive control group. Furthermore, both vaccine groups had higher HA-stem antibodies early after infection than the control group. In conclusion, immunization with VLPs displaying HA from antigenically distinct H1N1 variants increased the breadth of the immune response during subsequent H1N1pdm09 challenge, although this phenomenon was limited to intermediate antigenic variants.

Dataset Information

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Publications

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

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