The internal rotavirus protein VP6 primes for an enhanced neutralizing antibody response.

We studied in the rotavirus system whether the internal protein VP6 could prime for an enhancement in the production of neutralizing antibodies (NeuAb) against the external proteins, VP7 and VP4. It was found that BALB/c mice immunized with recombinant YM VP6 protein, and challenged i.p. with a heterologous rotavirus had an increase in the production of serum NeuAb compared to the control. This response was both homotypic and heterotypic, and involved an increase of NeuAb belonging to the IgM and IgG isotypes. Mice immunized with the recombinant VP6 and challenged orally with infectious murine rotavirus cleared the infection one day earlier than the control not immunized with VP6, and showed a small increase of total fecal anti-rotavirus IgA. The results suggest that the T-helper (Th) cells specific for VP6 can provide cognate help to B cells specific for neutralizing epitopes on the VP7 and/or VP4 molecules, and that this help can be heterotypic. Finally, we provide evidence that this phenomenon may be happening during infection.