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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Combination of three virus-derived nanoparticles as a vaccine against enteric pathogens; enterovirus, norovirus and
Suvi Heinimäki1, Minna M Hankaniemi2, Amir-Babak Sioofy-Khojine3
1Vaccine Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Insights
A novel vaccine combining norovirus (NoV), rotavirus (RV), and Coxsackie B virus (CVB) shows promise for preventing childhood gastroenteritis. The rVP6 component acts as an adjuvant, enhancing immune responses to CVB and supporting combination vaccine development.
Area of Science:
- Virology and Immunology
- Vaccine Development
Background:
- Enteric viruses like rotavirus (RV) and norovirus (NoV) cause significant childhood gastroenteritis, while enteroviruses (EV), such as Coxsackie B viruses (CVB), lead to severe neonatal disease.
- A non-live combination vaccine of NoV virus-like particles (VLPs) and RV rVP6 protein has shown protective immune responses and rVP6 demonstrated adjuvant properties for NoV VLPs.
Purpose of the Study:
- To investigate the feasibility of incorporating a third enteric virus antigen, specifically from CVB1, into the existing NoV-RV vaccine candidate.
- To evaluate the immunogenicity and potential adjuvant effects of adding CVB1 VLPs to the NoV-RV combination vaccine.
Main Methods:
- BALB/c mice were immunized twice with 10 µg of CVB1 VLPs, GII.4 VLPs, and rVP6 nanotubes, administered separately or in combination.
- The adjuvant effect of rVP6 on CVB1 responses was assessed by immunizing mice with 0.3 µg CVB1 VLPs with or without 10 µg rVP6.
- Humoral (serum IgG antibodies, isotypes) and cellular (IFN-γ secretion) immune responses, as well as neutralizing antibody activity, were measured.
Main Results:
- Comparable serum IgG antibody levels were achieved with single or combined antigen formulations.
- All formulations induced mixed Th2/Th1-type immune responses (IgG1 and IgG2a). The combination vaccine elicited unbiased Th1/Th2 responses to CVB1.
- Antisera demonstrated strong neutralizing activity against CVB1 and NoV GII.4. rVP6 exhibited an adjuvant effect on CVB1 responses, allowing for dose sparing and response homogenization.
Conclusions:
- The findings support the inclusion of additional enteric virus antigens, like CVB1, in combination vaccines to broaden protection against severe childhood infections.
- The rVP6 nanostructures confirm their adjuvant capabilities for enterovirus antigens, enhancing the potential of multivalent enteric virus vaccines.
Abstract:
Enteric viruses cause diverse infections with substantial morbidity and mortality in children, rotavirus (RV) and norovirus (NoV) being the leading agents of severe pediatric gastroenteritis. Coxsackie B viruses (CVB) are common enteroviruses (EV), associated with increased incidence of severe neonatal CVB disease with potentially fatal consequences. To prevent majority of childhood gastroenteritis, we have developed a non-live NoV-RV combination vaccine consisting of NoV virus-like particles (VLPs) and RV oligomeric rVP6 protein that induced protective immune responses to NoV and RV in mice. Moreover, rVP6 acted as an adjuvant for NoV VLPs. Here, we investigated a possibility to include a third enteric virus-derived antigen in the candidate NoV-RV vaccine, by adding recombinant nanoparticles derived from EV CVB1. To examine immunogenicity of EV-NoV-RV vaccine, BALB/c mice were immunized intramuscularly twice with 10 µg CVB1 VLPs, GII.4 VLPs and rVP6 nanotubes, either separately or combined. To evaluate the adjuvant effect of rVP6 on EV responses, mice received 0.3 µg CVB1 VLPs with or without 10 µg rVP6. Comparable serum IgG antibodies were detected whether the antigens were administered separately or in combination. Each formulation generated IgG1 and IgG2a antibodies, indicating a mixed Th2/Th1-type response. CVB1 VLPs skewed the isotype distribution slightly towards IgG1 subtype, while EV-NoV-RV combination vaccine induced unbiased Th1/Th2 responses to CVB1. Each antigen also induced T cell mediated immunity measured by IFN-γ secretion to specific stimulants ex vivo. Antisera raised by single antigens and combined formulation also exhibited strong neutralizing ability against CVB1 and NoV GII.4. Further, rVP6 showed an adjuvant effect on CVB1 responses, sparing the VLP dose and homogenizing the responses. Finally, the results support inclusion of additional antigens in the candidate NoV-RV combination vaccine to combat severe childhood infections and confirm adjuvant effect of rVP6 nanostructures.
