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Background. In a study performed in 1983, 18 adult volunteers received oral challenge with the virulent human rotavirus strain D (G1P1A[8],NSP4[B]). To identify correlates of resistance to rotavirus infection, we analyzed levels of serum immunoglobulin (Ig) A and IgG antibodies to various rotaviral antigens in 16 of the 18 volunteers. Methods. We used immunocytochemical assays that involved a total of 16 different recombinant baculoviruses, with each baculovirus expressing one of the following major serotype/genotype rotavirus proteins for the serologic assays: (1) viral protein (VP) 4 with P1A[8], P1B[4], P2A[6], P3[9], or P4[10] specificity; (2) VP7 with G1-G4 or G9 specificity; and (3) nonstructural viral protein (NSP) 4 with genotype A, B, C, or D specificity. Results. The prechallenge titers of IgG antibody to VP7 types G1, G3, G4, and G9; VP4 types P1A[8], P1B[4], P2A[6], and P4[10]; and NSP4 type [A] in the group of noninfected volunteers (n = 11) were significantly higher than those in the group of infected volunteers (n = 5; of these 5 volunteers, 4 were symptomatically infected). Moreover, logistic regression analysis showed that resistance to rotavirus infection most closely correlated with higher prechallenge titers of IgG antibody to homotypic VP7 (G1) and VP4 (P1A[8]). Conclusions. These results suggest that protection against rotavirus infection and disease is primarily VP7/ VP4 homotypic and, to a lesser degree, heterotypic.

In this issue of the Journal, the report by Banerjee et al. [1] on the postneonatal protective effect of a prior neonatal infection with G10P [11] 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 diarrhealillnesses postneonatally than did control children [2]. The available strains causing neonatal infection had identical electrophoretic patterns (in addition, 1 strain was identified as an "M-like" [G3] strain [3, 4]), 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 pro

There is an urgent need for a rotavirus vaccine, because up to 592,000 infants and young children

Homotypic and heterotypic serum isotype-specific antibody responses to rotavirus enterotoxin nonstructural protein (NSP)-4, independent neutralization antigens viral protein (VP)-4 and VP7, and group A rotavirus common antigen VP6 were analyzed by an immunocytochemistry assay in infants who received 1 of several live oral rotavirus vaccines. Significant serum immunoglobulin (Ig) A and IgG antibody responses to homotypic and/or heterotypic NSP4s of genotype [A], [B], or [C] were detected after vaccination. The magnitude of antibody responses to homotypic and heterotypic NSP4s was not significantly different, irrespective of the NSP4 genotype of the administered vaccine strain. In addition, there were no significant differences between IgA antibody responses to homotypic and heterotypic VP7s. In contrast, IgA antibody responses to VP4 were predominantly homotypic. IgA antibody responses to VP7 were lower in magnitude than those to VP4 but were comparable to those to NSP4. Antibody titers to homotypic and/or heterotypic NSP4s were positively correlated with those to VP6 before and after vaccination.

During a phase 3 clinical trial of rhesus monkey rotavirus-based quadrivalent vaccine in Venezuela, 2207 infants received 3 oral doses of vaccine (4 x 105 plaque-forming units/dose) or placebo at ages approximately 2, 3, and 4 months; 219 (14%) of 1537 stools obtained during 1550 diarrheal episodes in postvaccination surveillance were rotavirus-positive by enzyme-linked immunosorbent assay. With the use of various VP7 and VP4 primers for genotyping purposes, 213 of 219 rotavirus-positive stools were analyzed by reverse-transcription polymerase chain reaction. Twenty-nine (14%) of 213 rotavirus-positive stools contained at least 2 distinct rotavirus strains: a low-titered vaccine strain(s) and a second strain that, when possible, was studied further and found to be a wild-type rotavirus strain. The titer of vaccine viruses in 19 stools that plaqued directly in cell cultures ranged from 10(1) to 10(3) plaque-forming units/0.5 mL of a 10% stool suspension. Reassortants of vaccine virus and wild-type human rotavirus were not detected.

Live oral rhesus-rhesus-human rotavirus reassortant tetravalent (RRV-TV) vaccine was efficacious against rotavirus gastroenteritis but was withdrawn because of a rare association with intussusception. A corresponding tetravalent (types G1, G2, G3, and G4) reassortant vaccine based on bovine-human (UK) rotavirus reassortant tetravalent (BRV-TV) vaccine was developed concurrently.Before the withdrawal of RRV-TV vaccine, parallel placebo-controlled trials of BRV-TV vaccine (observer blinded) versus RRV-TV vaccine (double blinded) with a 2 : 1 ratio of vaccine : placebo were conducted in Finland in a total of 510 infants. Two doses of study vaccine or placebo were administered at ages 3 and 5 months.The first dose of RRV-TV vaccine was followed by a significant excess rate of febrile reactions (36%), whereas the rate of fever after the administration of BRV-TV vaccine did not differ significantly from that in the placebo group. Neither vaccine induced diarrhea. A seroresponse was detected in 97% of BRV-TV vaccine recipients and 94% of RRV-TV vaccine recipients. Both vaccines were equally effective, with 68%-69% efficacy against any and 88%-100% efficacy against severe rotavirus gastroenteritis during the first epidemic season.BRV-TV vaccine is a promising new candidate rotavirus vaccine, with low reactogenicity and high efficacy. Two doses of BRV-TV or RRV-TV vaccine are sufficient for the induction of protection against severe rotavirus disease.

A total of 16 different strains of rotavirus derived from seven mammalian species (four each from human and porcine species, two each from equine and simian species, and one each from canine and bovine species) and two avian species (one each from turkeys and chickens) were examined in plaque-reduction neutralization tests. Seven antigenically distinct serotypes were established on the basis of a greater than or equal to 20-fold difference between titers of homologous and heterologous reciprocal neutralizing antibodies. Serotypes 1 (strain Wa) and 2 (strain DS-1) were recovered only from humans. Serotype 3 included human rotavirus strain WALK 57/14, rhesus monkey rotavirus strain MMU18006 , vervet monkey rotavirus strain SA-11, dog rotavirus strain CU-1, and horse rotavirus strain H-2. The newly established serotype 4 was identified in both humans (strain St. Thomas no. 4) and pigs (strains Gottfried , SB-1A, and SB-2). Porcine (strain OSU ) and equine (strain H-1) rotaviruses made up a possible fifth serotype. Bovine rotavirus (strain NCDV) constituted a sixth serotype, and chicken rotavirus (strain Ch 2), which had a prime-strain relation with turkey rotavirus (strain Ty 1), was designated serotype 7. A surprising observation that emerged from this study was the existence of a rotavirus (porcine strain SB-1A) bridging serotypes 4 and 5.