To Serotype or Not To Serotype: That Is Still the Question

In this issue of the Journal, the report by Banerjee et al. on the postneonatal protective effect of a prior neonatal infection with G10P rotavirus has important implications for rotavirus vaccinology. The protective efficacy of a neonatal rotavirus infection has been addressed previously by various investigators. In a 1983 Australian study, neonates with asymptomatic rotavirus shedding during the first 14 days of life developed fewer and lesssevere rotavirus-positive diarrheal illnesses postneonatally than did control children. The available strains causing neonatal infection had identical electrophoretic patterns (in addition, 1 strain was identified as an “M-like” [G3] strain), whereas the strains causing postneonatal infection had varying patterns. Although serotypic characterization was not readily available at the time, evidence now indicates that asymptomatic neonatal G3 infections protected against community rotavirus strains, including heterotypic serotype G1 and G2 strains, during the 3-year period of surveillance.

Two groups set out to confirmthis concept by comparing the incidence of postneonatal rotavirus illnesses in a cohort of infants infected during the neonatal period with a G9 rotavirus strain 116E or with a G10P strain I321, the latter strain being similar to the neonatal strain described by Banerjee et al. in this issue of the Journal. These studies also found that a neonatal infection induced protection against postneonatal rotavirus illnesses. Data on protection against specific serotypes were not available; however, in the study on strain I321, the postneonatal strains had varying electrophoretic patterns, suggesting heterotypic protection.

A variety of other longitudinal studies of children, beginning at birth and extending up to 3 years of age, have examined the protective efficacy of a primary rotavirus infection against subsequent rotavirus exposure. However, the degree of protection was found to be inconsistent, ranging from none to substantial. Substantial protection was exemplified by a Mexican study in which a single rotavirus infection induced 87% protection against moderate-to-severe rotavirus-positive diarrhea, and 2 infections induced 100% protection. When a second infection occurred, the serotype responsible tended to be different from the original infecting strain. Moreover, high titers of serum anti-rotavirus antibodies, particularly IgA, were associated with protection against rotavirus infection and moderateto- severe diarrhea.

The protective role of preexisting, naturally acquired homotypic and heterotypic rotavirus antibodies was addressed in a study in a home for infants in Japan. A relatively high level of neutralizing antibodies against the infecting serotype was highly protective, whereas neutralizing antibodies against heterotypic strains provided much less or no protection, indicating that homotypic antibodies were a major correlate of protection in this study

The protective effect of neonatal infection on postneonatal illness also has been addressed in vaccine studies in Finland, where neonatal vaccination with a monovalent bovine Nebraska calf diarrhea virus vaccine (NCDV; G6P6) modified the severity of rotavirus illness and a single dose of tetravalent rhesus rotavirus- based tetravalent (RRV-TV) vaccine (a Rotashield precursor) given to neonates protected against fever associated with a second dose of RRV-TV vaccine at 2 months of age.