Rotavirus spike protein ΔVP8* as a novel carrier protein for conjugate vaccine platform with demonstrated antigenic potential for use as bivalent vaccine

Abstract

Conjugate vaccine platform is a promising strategy to overcome the poor immunogenicity of bacterial polysaccharide antigens in infants and children. A carrier protein in conjugate vaccines works not only as an immune stimulator to polysaccharide, but also as an immunogen; with the latter generally not considered as a measured outcome in real world. Here, we probed the potential of a conjugate vaccine platform to induce enhanced immunogenicity of a truncated rotavirus spike protein ΔVP8*. ΔVP8* was covalently conjugated to Vi capsular polysaccharide (Vi) of Salmonella Typhi to develop a bivalent vaccine, termed Vi-ΔVP8*. Our results demonstrated that the Vi-ΔVP8* vaccine can induce specific immune responses against both antigens in immunized mice. The conjugate vaccine elicits high antibody titers and functional antibodies against S. Typhi and Rotavirus (RV) when compared to immunization with a single antigen. Together, these results indicate that Vi-ΔVP8* is a potent and immunogenic vaccine candidate, thus strengthening the potential of conjugate vaccine platform with enhanced immune responses to carrier protein, including ΔVP8*.

Using Species a Rotavirus Reverse Genetics to Engineer Chimeric Viruses Expressing SARS-CoV-2 Spike Epitopes

“…To investigate the feasibility of using RV as an expression vector, we analyzed the effect of introducing SARS-CoV-2 spike peptides into the “head” region of the VP4 (i.e., VP8* domain), outside the sialic acid binding domain. Since VP8* is used in several vaccine platforms such as protein subunit or nanoparticle vaccines to induce RV-specific neutralizing antibodies ( 73 – 78 ), we hypothesized that the expression of SARS-CoV-2 spike peptides by VP8* may similarly generate neutralizing antibodies. However, incorporation of various spike epitopes into the VP8* lectin domain between amino acid positions 164 to 198 consistently showed significant decrease in viral titers, despite having no obvious effect on the rescue efficiency ( Fig.…”

Comparative whole genome analysis reveals re-emergence of typical human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi

“…Emerging virus strains have been associated with mutations that render vaccines and other therapies, such as monoclonal antibodies, less effective as seen with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Starr et al 2021). Previous studies have shown that the VP5* and VP8* outer capsid proteins play a significant role in inducing neutralising antibodies against rotaviruses (Ludert et al 2002; Park et al 2021; Ruggeri and Greenberg 1991; Zhao et al 2015). The VP5* protein of the Malawian G3P[8] strains were 100% conserved when compared to that of Rotarix vaccine, consistent with previous studies that have reported that the VP5* is a highly conserved protein (Rasebotsa et al 2020; Mwangi et al 2020).…”

Engineering a Vaccine Platform using Rotavirus A to Express SARS-CoV-2 Spike Epitopes

“…VP8* domain), outside the sialic acid binding domain. Since VP8* is used in several vaccine platforms such as protein subunit or nanoparticle vaccines to induce RV-specific neutralising antibodies [81][82][83][84][85][86], we hypothesised that the expression of SARS-CoV-2 spike peptides by VP8* may similarly generate neutralising antibodies. However, incorporation of various spike epitopes into the VP8* lectin domain between amino acid positions 164 -198 consistently showed significant decrease in viral titres, despite having no obvious effect on the rescue efficiency (Fig.…”