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SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.

ABSTRACT: Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain-hepatitis B surface antigen virus-like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>10⁴) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log₁₀) and nasal mucosa (~2.9 log₁₀) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.

SUBMITTER: Dalvie NC

PROVIDER: S-EPMC8926328 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.

Dalvie Neil C NC Tostanoski Lisa H LH Rodriguez-Aponte Sergio A SA Kaur Kawaljit K Bajoria Sakshi S Kumru Ozan S OS Martinot Amanda J AJ Chandrashekar Abishek A McMahan Katherine K Mercado Noe B NB Yu Jingyou J Chang Aiquan A Giffin Victoria M VM Nampanya Felix F Patel Shivani S Bowman Lesley L Naranjo Christopher A CA Yun Dongsoo D Flinchbaugh Zach Z Pessaint Laurent L Brown Renita R Velasco Jason J Teow Elyse E Cook Anthony A Andersen Hanne H Lewis Mark G MG Camp Danielle L DL Silverman Judith Maxwell JM Nagar Gaurav S GS Rao Harish D HD Lothe Rakesh R RR Chandrasekharan Rahul R Rajurkar Meghraj P MP Shaligram Umesh S US Kleanthous Harry H Joshi Sangeeta B SB Volkin David B DB Biswas Sumi S Love J Christopher JC Barouch Dan H DH

Science advances 20220316 11

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain-hepatitis B surface antigen virus-like particle eli ...[more]

PMID: 35294244

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Project description:BackgroundMucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, we have a limited understanding about the antibodies present on the nasal mucosal surfaces.MethodsIn this study, we evaluated SARS-CoV-2 mucosal antibodies following previous infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 143 individuals, which include convalescent, vaccinated, or breakthrough infections.FindingsWe detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. Depletion of IgA antibodies in nasal fluids resulted in a tremendous reduction of neutralization activity against SARS-CoV-2, indicating that IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against SARS-CoV-2 was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants.InterpretationIn summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates higher titers of binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies.FundingThe work was funded by the COVID-19 National Research Program 78 (grant number 198412) of the Swiss National Science Foundation.

Dataset Information

SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.

Publications

SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.

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