Identification of Cross-Reactive Norovirus CD4 ⁺ T Cell Epitopes

Multiple Antigenic Sites Are Involved in Blocking the Interaction of GII.4 Norovirus Capsid with ABH Histo-Blood Group Antigens

“…In this regard, the S/P (S domain from one genogroup and P domain from another) chimeric norovirus VLPs might present the advantage of inducing broadly reactive immune responses and thus may constitute a new platform for norovirus VLP-based vaccines. It has been shown that the CD4 ϩ epitopes are located in different domains of VLPs, depending on the norovirus strain (41). Thus, even though it is believed that most B cell neutralizing epitopes might be located in the P domain of the capsid, the presence of T cell epitopes in the S domain suggests that vaccination with S/P chimeric VLPs might enhance the immune response and cross-protection against different genogroups.…”

Norovirus vaccines: Correlates of protection, challenges and limitations

“…Defining and identifying specific T cell epitopes of NoV capsids are important to understand the antigenic and immunogenic relationships of different viral strains. This has been demonstrated to be critical in the mice model 103 whereby cross-reactive NoV CD4 C T cell epitopes were identified. Vaccine studies might need to characterize major NoV abbinding epitopes, a critical factor to prevent the emergence of antigenic variants.…”

“…The same group reported however that a tetravalent form of the vaccine containing GI.1, GII.1, GII.2 and GII.4 was less efficient at stimulating a broad antibody response. 103 While many experimental vaccine designs have used the murine model, a number of concerns remain in place in the results presented above: 1) the different disease biology between mice and humans whereby only immunocompromised mice clinically manifest diarrhea as demonstrated by severe illness following MNV infection among innate-immunity-deficient mice (IFN-a/b and IFN-g receptor-deficient) 114 ; 2) the difficulty in extrapolating the clearance of MNV from the intestines to the possible physiological results in humans; 3) MNV does not use HBGA for attachment and is characterized by little genetic and antigenic variation. 115 Nevertheless, the mouse model is still a convenient and a cost effective platform for potential NoV vaccine studies.…”

“…Vaccines have been engineered to include components representing different variants/and or strains in an attempt to generate broadly reactive immune responses against different NoV strains. Bivalent 113 and multivalent vaccines with NoV components 76,103,105 were tested along with bivalent [109][110][111] and trivalent forms 112 with non-NoV representation ( Table 1). The main results of these studies show the stimulation of cross-reactive humoral immune responses in the animal model.…”

“…. 103 Splenocytes from mice immunized with live MNV were stimulated in vitro with a panel of VLPs containing overlapping 15-mers peptides spanning the NoV GI.1 and GII.4 capsids. CD4 C T cells were able to secrete IFN-g following homotypic but not heterologous in vitro stimulation with human NoV VLPs.…”