Immunogenicity of the pentavalent rotavirus vaccine among infants in two developing countries in Asia, Bangladesh and Vietnam
ABSTRACT Background: We evaluated the immunogenicity of the pentavalent rotavirus vaccine (PRV) in two GAVIeligible
Asian countries, Bangladesh and Vietnam, nested in a larger randomized, double-blind, placebocontrolled
efficacy trial conducted over a two-year period from 2007 through 2009.
Methods: 2036 infants were randomly assigned, in a 1:1 ratio, to receive three oral doses of PRV or
placebo approximately at 6, 10, and 14 weeks of age. Concomitant use of EPI vaccines, including oral
poliovirus vaccine (OPV) and diphtheria-tetanus-whole cell pertussis (DTwP) vaccine, was encouraged
in accordance to the local EPI schedule. A total of 303 infants were evaluated for immunogenicity and
blood samples were collected before the first dose (pD1) and approximately 14 days following the third
dose (PD3). The seroresponse rates (≥3-fold rise from pD1 to PD3) and geometric mean titers (GMTs)
were measured for anti-rotavirus immunoglobulin A (IgA) and serum neutralizing antibody (SNA) to
human rotavirus serotypes G1, G2, G3, G4, and P1A, respectively.
Results: Nearly 88% of the subjects showed a
≥3-fold increase in serum anti-rotavirus IgA response in
the analysis of the two countries combined. When analyzed separately, the IgA response was lower in
Bangladeshi children (78.1% [95% CI: 66.0, 87.5]) than in Vietnamese children (97.0% [95% CI: 89.6, 99.6]),
with a PD3 GMT of 29.1 (units/mL) and 158.5 (units/mL), respectively. In the combined population, the
SNA responses to the individual serotypes tested ranged from 10 (G3) to 50 (G1) percentage points lower
than the responses shown in the developed countries. However, the SNA response to G3 in Vietnamese
subjects was 37.3% (95% CI: 25.8, 50.0), which was similar to the G3 response rate in developed countries.
Conclusions: Three oral doses of PRV were immunogenic in two GAVI-eligible Asian countries: Bangladesh
and Vietnam. The GMTs of both the serum anti-rotavirus IgA and SNA responses were generally higher
in Vietnamese than in Bangladeshi children. The SNA responses varied by individual serotypes and were
lower than the results from developed countries. The clinical significance of these observations is not
understood because an immune correlate of protection has not been established.
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ABSTRACT: Background Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. Methods This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6–8, 10–12 and 14–16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. Results Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 105.0 FFU, 105.8 FFU, 106.4 FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 106.4 FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. Conclusions Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose–response) in healthy Indian infants.Vaccine. 01/2014; 32:A117–A123.
- Vaccine 04/2012; 30 Suppl 1:A1-2. · 3.77 Impact Factor