A SARS-CoV-2 and influenza double hit vaccine based on RBD-conjugated inactivated influenza A virus

Author:

Wang Zhenzhen12ORCID,Li Zhenhua12ORCID,Shi Weiwei12ORCID,Zhu Dashuai12ORCID,Hu Shiqi12ORCID,Dinh Phuong-Uyen C.12ORCID,Cheng Ke123ORCID

Affiliation:

1. Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.

2. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, NC 27606, USA.

3. Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

The circulating flu viruses merging with the ongoing COVID-19 pandemic raises a more severe threat that promotes the infectivity of SARS-CoV-2 associated with higher mortality rates. Here, we conjugated recombinant receptor binding domain (RBD) of SARS-CoV-2 spike protein onto inactivated influenza A virus (Flu) to develop a SARS-CoV-2 virus-like particle (VLP) vaccine with two-hit protection. This double-hit vaccine (Flu-RBD) not only induced protective immunities against SARS-CoV-2 but also remained functional as a flu vaccine. The Flu core improved the retention and distribution of Flu-RBD vaccine in the draining lymph nodes, with enhanced immunogenicity. In a hamster model of live SARS-CoV-2 infection, two doses of Flu-RBD efficiently protected animals against viral infection. Furthermore, Flu-RBD VLP elicited a strong neutralization activity against both SARS-CoV-2 Delta pseudovirus and wild-type influenza A H1N1 inactivated virus in mice. Overall, the Flu-RBD VLP vaccine is a promising candidate for combating COVID-19, influenza A, and coinfection.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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