IS A RHINOVIRUS VACCINE POSSIBLE?

Abstract

Renewal of support for efforts to develop a rhinovirus vaccine seems justified in the light of newer epidemiologic and immunologic studies. The major contribution of RV to acute upper respiratory disease in all age groups but especially in young children emphasizes the public health importance of an effective vaccine. Epidemiologic surveillance of RV infections in widely separated areas has identified two relevant phenomena. First, in each area, certain serotypes were more frequently encountered and tended to persist. Such "common" serotypes accounted for a disproportionate share of the infections recognized and, hence, constitute special targets for immunization. Second, a clear increase over time in the proportion of RV isolates representing higher numbered (types 56-89) serotypes or untypable strains (potentially new serotypes) suggests that new serotypes continue to emerge as the result of progressive antigenic shift. The common origin of the multitudinous RV serotypes so suggested is consistent with the extensive antigenic cross-relations which are becoming evident. Systematic cross-testing with monospecific antisera, especially when high titer sera are employed, has revealed an appreciable number of one-way and reciprocal relations. Largely fortuitous observations of naturally or experimentally infected humans have revealed many additional cross-relations manifested by concurrent response to heterologous RV and presumably attributable to sensitizations resulting from prior RV infections. A model for this has been provided by rabbits immunized sequentially with different potent RV immunogens. Available information as displayed in figure 2 indicates that extensive cross-relations do exist and that sizeable groups of closely related serotypes may be identified. More intensive search for heterotypic response to infection of man coupled with selective use of the rabbit model should define the full extent and strength of cross-relations and identify completely the more closely related groups of serotypes as the basis for formulation of a broadly effective RV vaccine containing a limited number of serotypes. The cross-relations described are based entirely on development of serum neutralizing antibody, the presence of which in man is clearly correlated with relative protection against infection and disease. While this protection may well prove to be mediated largely by concomitant nasal secretory antibody, it is not unreasonable to expect that the antigenic cross-relations also would be manifested in secretory antibody response. These important questions concerning secretory antibody can be best explored in a limited series of volunteer trials with selected cross-related RV serotypes in which homotypic and heterotypic protection could be correlated with serum and nasal secretory antibody. The state of current knowledge, as I view it, is sufficient to justify initiation of such trials at any time.