Rotaviruses: Immunological Determinants of Protection Against Infection and Disease

Offit, Paul A.

Publisher Summary This chapter focuses on four important questions that remain unanswered: (1) what is the importance of virus serotype in formulating an optimal vaccine? (2) which immunological effector arm most likely protects against rotavirus disease? (3) by what means is virus antigen best presented to the host to elicit a protective immune response? (4) what are the advantages and disadvantages of replicating agents as compared to nonreplicating agents as candidate rotavirus vaccines? Although two proteins (vp4 and vp7) are probably important in inducing protection against challenge, it has not been clearly demonstrated that inclusion of the epidemiologically important human P or G type is important in protection against human disease. No immunological effector arm clearly explains protection against heterotypic challenge. Protection against disease is not predicted by rotavirus-specific neutralizing antibodies in serum. Oral inoculation may not be necessary to induce a protective, virus-specific immune response at the intestinal mucosal surface, but parenteral inoculation of experimental animals with rotavirus induces an immune response at the intestinal mucosal surface that is protective against challenge. Induction of a rotavirus-specific protective immune response is probably associated with the presence of virus-specific T and B cells in intestinal lymphoid tissues and virus-specific sIgA or IgG at the intestinal mucosal surface. There is some experimental evidence to support the hypothesis that neither rotavirus replication nor presentation of rotavirus antigen to the intestinal mucosal surface is necessary to achieve this aim.