Immunization with one alphavirus cross-primes cellular and humoral immune responses to a second alphavirus.

Abstract

Abstract The kinetics of appearance and specificity of T and B cell responses to alphavirus-infected cells and virions were monitored after inoculation of C3H mice with Sindbis (SIN) or Semliki Forest (SF) virus. One or two sequential inoculations with a single alphavirus elicited cytotoxic T cell (CTL) responses that cross-reacted equally well with syngeneic L929 cells infected with either the homologousimmunizing or the heterologous-challenging alphavirus. In contrast, one or two inoculations with a single alpha-virus elicited a specific humoral response only to that virus, whether measured against virion antigens by neutralization or against virus-infected cells by antibody-dependent, complement-mediated cytotoxicity (ADCMC). However, when a heterologous alphavirus was inoculated into immunized mice, the resulting ADCMC response to cells infected with the challenge virus was greater than that obtained by challenge of sham-immunized mice, and the ADCMC response to cells infected with the original immunizing alphavirus was also enhanced. Both enhanced humoral responses were detected only in assays using virus-infected cells (ADCMC) but not in neutralization or hemagglutination inhibition assays (1) using virions. Furthermore, heterologous alphavirus stimulation induced a significantly higher CTL response to cells infected with either the immunizing or the challenge virus than CTL responses observed after one or two inoculations of a single alphavirus. The results suggest that a single immunization with one alphavirus elicits a virus-specific humoral response and a cross-reactive T cell response while simultaneously cross-priming the immune system for a humoral response to the heterologous virus and an enhanced T cell response to either virus. Furthermore, it appeared that cross-priming could be detected only after heterologous virus challenge and only in assays that measured reactivity to viral antigens present on infected cells.