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The G1P1A[8] rotavirus vaccine candidate 89-12, the precursor to Rotarix, stimulated high titers of neutralizing antibodies to non-G1/P1A[8] serotypes of human rotavirus in naturally infected subjects before attenuation by cell-culture passages. These responses were greatly diminished in young infants (median age, 11 weeks) administered the attenuated vaccine. Because of the possibility of improved responses in older infants, the immunogenicity of the 89-12 vaccine candidate was evaluated after administration of 2 doses beginning at either 4 or 6 months of age. As was found in young infants, neutralizing antibody responses to non-G1/P1A[8] rotaviruses were considerably lower than those observed after natural infection. The reasons identified were overall (P

A quadrivalent precursor to the pentavalent rotavirus vaccine candidate RotaTeq was evaluated in a 3-dose, 439-subject study. To determine immunogenicity, the quantity of rotavirus immunoglobulin A (IgA) in stool specimens obtained, at 1 of 10 study sites, from 37 placebo and 37 vaccine recipients was measured. None of the placebo recipients showed a clinically important (>/=3-fold) increase in stool rotavirus IgA, whereas 31 vaccine recipients showed an increase after at least 1 dose of vaccine. In total, 16, 19, and 15 vaccine recipients had increases after 1, 2, and 3 doses, respectively, indicating that a 3-dose regimen increased the immune response elicited by this vaccine.

Summary Background Rotavirus is the most common cause of severe, dehydrating diarrhoea in infants worldwide. We assessed the safety, immunogenicity, and efficacy of a live, oral human rotavirus vaccine, 89–12, in US children in a randomised, placebo-controlled, double-blind multicentre trial. Methods 215 healthy infants were enrolled, of whom 213 were given two doses of 89–12 (containing 1×10 5 plaque-forming units) or placebo, and 213 were followed up through one rotavirus season. The frequency of side-effects was compared for 7 days after each dose of vaccine. Immune responses to rotavirus were assessed by serum and stool IgA, and by serum 89–12 neutralising titres. The primary outcome variable (protection from rotavirus disease) was evaluated by comparing the frequencies of rotavirus gastroenteritis in an intention-to-treat analysis. Findings Adverse reactions were mild. Low-grade fever (≥38·1°C) after the first dose was the only side-effect significantly more common in the vaccine group than in the placebo group (21 [19%] vs 5 [5%], p=0·001). An immune response to vaccine was detected in 94·4% of vaccinees. Rotavirus disease occurred in 18 of 107 placebo recipients and two of 108 vaccine recipients (vaccine efficacy 89·0% [95% Cl 65·4–94·5]). Ten infants in the placebo group but none in the vaccine group were presented for medical care. Interpretation The 89–12 rotavirus vaccine was safe and immunogenic and provided a high degree of protection against rotavirus disease. Further investigations of this vaccine are needed to confirm these findings in other settings.

The safety and immunogenicity of an orally administered live human rotavirus vaccine candidate (89-12), attenuated by 33 passages in monkey kidney cells, were evaluated in placebo-controlled trials in adults, children and infants. This strain was selected because natural infections with 89-12-like rotaviruses provided 100% protection over two years. The initial evaluations in adults, seropositive children and nine infants indicated that the vaccine was safe. Two doses of vaccine (10(5) p.f.u. dose-1) or placebo were then given to 42 infants, aged from 6 to 26 weeks. No significant difference in side effects was seen. Seroconversion was demonstrated in 19 of 20 previously uninfected vaccine recipients, but > or = 4-fold rises in 89-12 neutralizing antibody titers were detected in only seven subjects. Intestinal IgA responses were detected in 15 subjects. This attenuated human rotavirus was safe and immunogenic and should be further evaluated as a vaccine candidate.

The safety and immunogenicity of a booster dose of a new acellular pertussis component diphtheria-tetanus toxoids-pertussis vaccine (DTaP) were compared with whole cell pertussis component diphtheria-tetanus toxoids-pertussis vaccine (DTwP). Fifty children ages 15 to 18 months and 50 children ages 4 to 6 years were studied. The incidence of adverse reactions observed during the first 72 hours after vaccination in the DTaP/DTwP vaccinees were: pain, 32%/92% (P0.001); redness, 14%/24% (P = 0.2); swelling, 2%/14% (P0.03); fever, 52%/90% (P0.001); drowsiness, 14%/34% (P0.05); fussiness, 32%/88% (P0.001); and unusually poor appetite, 6%/42% (P0.001). The geometric mean titers of anti-pertussis toxin and anti-filamentous hemagglutinin antibody were also significantly (P0.001) higher in the DTaP compared to the DTwP recipients. When administered as a booster dose this DTaP vaccine, which has been chosen by the NIH for the second pertussis vaccine clinical efficacy trial, was more immunogenic for pertussis toxin and filamentous hemagglutinin and caused fewer and less severe adverse reactions compared with the Connaught DTwP vaccine used in this study.

To measure protection induced by natural rotavirus infection, 163 infants enrolled in a rotavirus vaccine trial were prospectively followed for 2 years. Serotype 1 rotaviruses were the predominant circulating strains during the study. Over the 2 years of observation, significantly fewer infants infected before enrollment developed a symptomatic reinfection (0 of 21) or any reinfection (4 of 21) compared with previously uninfected infants (P = .0003). Of the 60 infants who developed a primary rotavirus infection in the first year (40 symptomatic, 20 asymptomatic) only 4 were reinfected in the second year compared with 29 of 82 subjects not previously infected (P = .00003). Asymptomatic primary infection appeared to be as protective as symptomatic primary infection. The only symptomatic reinfections occurred in 2 subjects who did not develop rotavirus antibody after the initial detection of rotavirus. An age-related reduction in the ratio of symptomatic to asymptomatic primary rotavirus infection was also detected. In this study, protection against homotypic serotype 1 reinfection appeared to last greater than or equal to 2 years.