Immunity to homologous rotavirus infection in adult mice: response.

Firstly, we would like to express our appreciation to Franco and Greenberg for highlighting the possibilities and limitations associated with this particular model system. As they point out, since we first developed the model and published our first article on its use1xDevelopment of an adult mouse model for studies on protection against rotavirus. Ward, R.L. et al. J. Virol. 1990; 64: 5070–5075PubMedSee all References1, it has been used by many labs with a variety of mouse and rotavirus stains. Therefore, conclusions drawn with any specific mouse and/or rotavirus set cannot immediately be generalized to other sets. However, if information is not available or cannot be obtained with other sets owing to, for example, a lack of appropriate genetically deficient mouse strains on a particular mouse background, extrapolating the results to the broader picture is a natural course of events. When this is done, the caveats should also be discussed. A case in point is our observation that, following intranasal immunization with either double-layered rotavirus particles2xAntibody-dependent and -independent protection following intranasal immunization of mice with rotavirus particles. McNeal, M.M. et al. J. Virol. 1999; 73: 7565–7573PubMedSee all References2 or VP6 proteins3xAntibody-independent protection against rotavirus infection of mice stimulated by intranasal immunization with chimeric VP4 or VP6 protein. Choi, A.H-C. et al. J. Virol. 1999; 73: 7574–7581PubMedSee all References3, together with LT(R192G) as an adjuvant, B-cell-deficient μMt mice with a C57BL/6 background are as protected from rotavirus strain EDIM infection as are immunologically normal BALB/c mice. Based on this result, we concluded that protection following intranasal immunization with VP6 in BALB/c mice was unlikely to be antibody dependent. Since that time, this conclusion has been supported by additional evidence (A.H-C. Choi et al., unpublished), namely that both protein fragments and peptides derived from VP6 that do not stimulate detectable serum or stool rotavirus antibodies following intranasal immunization induce nearly complete protection against EDIM shedding in BALB/c mice.To our knowledge, the suggestion by Franco and Greenberg that ‘protective mechanisms identified in C57BL/6 mice probably differ from those identified in BALB/c or 129 mice’ can be substantiated only with regard to innate immunity. Clearly, if the same quantity of a specific rotavirus strain is administered to different mouse strains they will shed very different quantities of virus in their stools. For example, in our laboratory, adult C57BL/6 mice administered either culture-adapted or unpassaged EDIM rarely shed detectable amounts of virus. By contrast, both BALB/c and 129 mice shed large quantities of EDIM when challenged as adults. Therefore, their abilities to withstand rotavirus infections as adults clearly differ. The reasons for this could be as simple as differences in available rotavirus receptors on intestinal epithelial cells. There appears to be no compelling evidence that this result regarding innate immunity can be directly extrapolated to conclusions concerning basic differences in mechanisms of learned immunity between mouse strains. However, we acknowledge that this possibility should not be overlooked.