Design of Nanoparticle-based Immunogens for Influenza and SARS-CoV-2

Abstract

Influenza and SARS-CoV-2 are viral pathogens responsible for causing respiratory illnesses in humans. Both have led to global pandemics in the past, resulting in significant mortality and morbidity. Vaccination has been effective in reducing infection and severity of both diseases. However, these viruses are known for their ability to undergo mutations that reduce vaccine efficacy, emphasizing the need for robust vaccines offering sustained protection. Analyzing the sequences of major surface antigens such as Influenza hemagglutinin (HA) and SARS-CoV-2 spike has identified regions containing neutralizing epitopes. Targeting these regions offers potential for developing potent vaccines effective against a range of variants. Additionally, utilizing self-assembling proteins as nanoparticle platforms can enhance the presentation of these antigens thus improving immune responses. Through nanotechnology and rational design, we have created nanoparticle-based immunogens displaying either the HA stem of Influenza or the Spike receptor binding domain (RBD) of SARS-CoV-2. We report the design of stable nanoparticle immunogens with appreciable thermal stability, antigenicity, and immunogenicity. In mouse models, these immunogens induce robust antibody responses which are superior to those elicited by soluble counterparts. A fraction of these induced antibodies is neutralizing in nature and confer cross-protection against drifted variants of influenza and SARS-CoV-2. In challenge studies with influenza virus, immunized mice showed protection from mortality when exposed to lethal doses of both homologous and heterologous viruses. This research underscores the potential of nanoparticle-based immunogens in developing next-generation vaccines with improved efficacy and conferring broad-spectrum protection against evolving viral threats.