Immunologic methods and correlates of protection.

Studies of natural rotavirus (RV) infection in children have shown that protection against subsequent RV disease occurs (1). Assessment of humoral immune responses has included study of the importance of circulating vs intestinal antibodies (Abs), serotype-specific vs group-specific Abs, and RV-specific immunoglobulins IgA, IgM, and IgG (1). Following natural RV infection, RV-specific IgM, followed by IgA and IgG, appear in serum and duodenal fluid or stool of young children (2). Protection against subsequent RV infection is predicted by the quantity of virus-specific IgA in the feces and serum (3, 4). In addition, virus-specific antibody-secreting cells (ASC) of the IgA, IgM, and IgG isotypes have been detected in the blood of infants following RV infection (5), although correlation between the presence of ASCs and protection against subsequent disease has not been studied. Serum neutralizing antibodies (nAbs) occur after natural RV infection in children, and are serotype-specific (4,6). Overall, protection against subsequent RV infection is correlated with higher titers of nAb (4). Protection against infection has been correlated with homotypic nAb to the G1 serotype (4); however, other studies suggest that protection is not dependent on serotype-specific nAb (7).

Upper airway obstruction in association with perinatally acquired herpes simplex virus infection.

Two cases of neonatal upper respiratory tract obstruction caused by herpes simplex virus are described. Infection of the upper respiratory tract with this virus should be included in the differential diagnosis of fever and stridor during the neonatal period.

Neutralizing antibodies to heterologous animal rotavirus serotypes 5, 6, 7, and 10 in sera from Ecuadorian children.

Serum samples from 870 Ecuadorian children who underwent natural rotavirus exposure were tested for neutralizing serum antibody to heterologous animal rotavirus (RV) serotypes. Six percent of the sera neutralized porcine RV OSU (serotype 5), 10% neutralized bovine RV NCDV (serotype 6), 4% neutralized avian RV Ch-2 (serotype 7), and 8% neutralized bovine RV V1005 (serotype 10). Neutralization was defined as a 90% reduction in infectious virus at a 1:100 serum dilution. The prevalence of antibody to all four heterotypic viruses increased with the age of the children and the number of human RV serotypes neutralized, but prevalences did not differ significantly between children from rural and urban areas of Ecuador. No serum sample that specifically neutralized bovine RV NCDV was identified. We inferred from the seroepidemiological analysis that human RVs contain immunorecessive neutralization epitopes that can stimulate cross-neutralizing antibody to heterotypic animal RVs. This occurs increasingly with age and with the number of human serotypes recognized by a child's neutralizing antibody. Thus, it appears that a broadened immune response to the heterotypic strains occurs with repetitive RV infections.

Polypeptide specificity of antiviral serum antibodies in children naturally infected with human rotavirus.

Reassortants between serotype 3 SA11 and serotype 6 NCDV rotaviruses were used to determine the relative amounts of serum-neutralizing antibody to VP4 and VP7 of serotype 3 SA11 rotavirus in children after natural rotavirus exposure. Sera from Ecuadorian children of a population-based study and sera from children of a hospital-based study in Germany (excluding diarrhea patients) demonstrated high titers of VP7-specific but only low titers of VP4-specific antibodies. In contrast, paired sera from German children hospitalized with a symptomatic primary rotavirus gastroenteritis demonstrated a titer increase to VP4 more frequently than to VP7 protein by neutralization test and immunoblotting. For these rotavirus patients, we provided, previously, direct evidence for the development of cross-neutralizing antibodies.