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

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.

COVID-19 Vaccines: Where Did We Stand at the End of 2023?

“…In the case of NDV-based vaccines, the next-generation trivalent NDV-HXP-S vaccines expressing the prefusion-stabilized S protein of the original SARS-CoV-2 strain, the gamma and delta variants significantly enhanced the protection against disease and provided cross-neutralizing antibodies against distant variants such as omicron [ 185 ]. In another approach, the inactivated influenza A virus (Flu) was conjugated with the recombinant SARS-CoV-2 S RBD, which generated SARS-CoV-2 virus-like particles (VLPs) [ 186 ]. The Flu-RBD VLPs induced strong neutralization activity against both wild-type SARS-CoV-2 and the delta variant.…”

Towards broad-spectrum protection: the development and challenges of combined respiratory virus vaccines

“…They anchored the SARS-CoV-2 RBD onto the inactivated influenza virus surface using a bio-orthogonal click reaction between dibenzo cyclooctyne (conjugated to viral envelop) and azido (linked to the RBD). In hamster model, two doses of this vaccine induced robust humoral and cellular immune responses, including viral-specific neutralizing antibodies, and offered protection against both pathogens, evidenced by reduced viral replication in the BALF and diminished lung lesions in the vaccinated hamsters (Wang et al, 2023). Pulkina et al developed an RSV vaccine by using the influenza vector platform.…”

A subunit‐based influenza/SARS‐CoV‐2 Omicron combined vaccine induced potent protective immunity in BALB/c mice

“…Also, COVID‐19 vaccination has effectively reduced severe cases and mortality rate 10,11 . Many dual‐vaccination strategies are currently in the developmental stage, such as the virion‐based vaccine, 12,13 receptor‐binding domain (RBD)‐based vaccine, 14 RBD‐conjugated inactivated IAV, 15 mRNA vaccine, 8 chimpanzee adenovirus 68 (AdC68)‐based vaccine, 16 and recombinant VSV‐based bivalent vaccine 17 . Similarly, we imagined the advantages of a combined SARS‐CoV‐2/IAV subunit vaccine in the fight against COVID‐19 and influenza, including the safety and ease of producing such subunit vaccine on a large scale.…”

“…9 Also, COVID-19 vaccination has effectively reduced severe cases and mortality rate. 10,11 Many dual-vaccination strategies are currently in the developmental stage, such as the virion-based vaccine, 12,13 receptor-binding domain (RBD)-based vaccine, 14 RBD-conjugated inactivated IAV, 15 mRNA vaccine, 8 chimpanzee adenovirus 68 (AdC68)-based vaccine, 16 and recombinant VSV-based bivalent vaccine. 17…”