Dataset Information

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

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.

SUBMITTER: Chandrashekar A

PROVIDER: S-EPMC8845420 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chandrashekar Abishek A Yu Jingyou J McMahan Katherine K Jacob-Dolan Catherine C Liu Jinyan J He Xuan X Hope David D Anioke Tochi T Barrett Julia J Chung Benjamin B Hachmann Nicole P NP Lifton Michelle M Miller Jessica J Powers Olivia O Sciacca Michaela M Sellers Daniel D Siamatu Mazuba M Surve Nehalee N VanWyk Haley H Wan Huahua H Wu Cindy C Pessaint Laurent L Valentin Daniel D Van Ry Alex A Muench Jeanne J Boursiquot Mona M Cook Anthony A Velasco Jason J Teow Elyse E Boon Adrianus C M ACM Suthar Mehul S MS Jain Neharika N Martinot Amanda J AJ Lewis Mark G MG Andersen Hanne H Barouch Dan H DH

bioRxiv : the preprint server for biology 20220207

<h4>Background</h4>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.<h4>Methods</h4>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 wer ...[more]

PMID: 35169798

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Project description:Mucosal immunity plays a pivotal role in providing comprehensive protection against upper-airway infections and effectively limiting the shedding and transmission of SARS-CoV-2. Despite its critical importance, there remains a notable absence of nasal spray vaccines endorsed for global use by the World Health Organization. This could be due to the inability of current intranasal vaccines to induce strong mucosal and systemic responses in humans, thus urgently entailing a next-generation of intranasal COVID-19 vaccines with novel and safe technologies. In this study, we prepared a two-component intranasal vaccine that combines adenovirus vectors with a self-assembled subunit protein. Specifically, the adenovirus vector expresses the spike protein of XBB.1.5 variant (Ad5XBB.1.5), and were mixed with the recombinant protein that developed derived from the receptor binding domain (RBD) of XBB.1.5 (RBDXBB.1.5-HR). Combination of Ad5XBB.1.5 and RBDXBB.1.5-HR elicited superior humoral and cellular immunity against XBB.1.5-included variants compared with the individual components. Importantly, the STING signaling pathway was found to be crucial for the adjuvant effect of the adenovirus vector. In addition, to increase the broad-spectrum neutralizing capacities, a trimeric protein derived from the BA.5 variant (RBDBA.5-HR) was incorporated to formulate a three-component vaccine (Ad5XBB.1.5+RBDXBB.1.5-HR+RBDBA.5-HR), indicating the utilization of a combination of an adenovirus-vectored and subunit protein vaccines has the potential to serve as a next-generation intranasal vaccine platform. Of note, intranasally delivery of two-component vaccine provided protective immunity against live Omicron XBB.1.16 virus challenge in mice. Furthermore, the combination of adenovirus and subunit protein vaccine demonstrates excellent tolerability and safety in human subjects, and is able to induce enhanced mucosal immunity as well as high levels of sera neutralizing antibody in all participants. These findings underscore its suitability for clinical application in the prevention of SARS-CoV-2 variants encompassing XBB lineages.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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