Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses

Mice Develop Effective but Delayed Protective Immune Responses When Immunized as Neonates either Intranasally with Nonliving VP6/LT(R192G) or Orally with Live Rhesus Rotavirus Vaccine Candidates

“…immunizations of chimeric EDIM VP6 protein combined with the adjuvant LT(R192G) 2 weeks apart and challenged 4 weeks later with EDIM, fecal shedding of rotavirus antigen was reduced Ͼ99% for at least 12 months relative to that found for unimmunized animals (13,16). We also reported that a single immunization was as effective as two or three in these animals.…”

“…The immunogens used in this study [VP6/LT(R192G) and RRV] were selected because both are vaccine candidates (16,35), both elicit nearly full protection against EDIM shedding when mice are challenged 6 weeks after vaccination (13,16,23,43), and both are delivered via mucosal surfaces. Intranasal immunization of 7-day-old mice with a single dose of VP6/ LT(R192G) elicited no protection against EDIM shedding when the mice were challenged prior to weaning at 17 days of age.…”

“…The J chain KO mice were shown to produce large quantities of both serum rotavirus IgG and IgA but no detectable stool rotavirus IgA (results not shown). Furthermore, serum antibodies generated in BALB/c mice after subcutaneous immunization with the G1P[3] D ϫ RRV reassortant strain readily neutralized RRV and the G1 Wa strain of rotavirus but were unable to neutralize the G3P [16] EDIM strain (Table 4). Likewise, serum antibodies generated after subcutaneous immunization of mice with EDIM were able to neu-…”

“…One candidate vaccine evaluated with this model is Escherichia coliexpressed VP6 protein. When administered either intranasally or orally together with attenuated E. coli heat-labile toxin LT(R192G), the expressed VP6 protein of the murine rotavirus strain EDIM provided nearly complete protection against EDIM shedding in adult mice (13,16). The mechanisms by which VP6/LT(R192G) elicits protection appear to differ from those for live virus immunization in this model.…”

Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4+T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G)

“…That is, protection is not dependent on B or CD8 ϩ T cells but, instead, CD4 ϩ T cells are the only lymphocytes required for protection, and this protection remains fully intact for many months, probably for the lifetime of the mouse (9,10,34). Although there is evidence that CD4 ϩ T cells may also be the only lymphocytes needed for protection against other viruses (11,22,23,35,37,41,54), antibodies and CD8 ϩ cytotoxic T cells are the most common effectors of protection against viral diseases, and the role of CD4 ϩ T cells is typically restricted to their helper functions.…”