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Systemic and mucosal immune responses to rhesus rotavirus vaccine MMU 18006
G A Losonsky1, M B Rennels, Y Lim
1Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.
Insights
This study evaluated the rhesus rotavirus vaccine MMU 18006 in infants. The vaccine successfully induced homotypic immunity to serotype 3 rotavirus, with 91% showing antibody seroconversion.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Rotavirus is a leading cause of severe diarrheal disease in infants globally.
- Development of effective rotavirus vaccines is crucial for public health.
- The rhesus rotavirus vaccine MMU 18006 contains a human rotavirus serotype 3 neutralization antigen.
Purpose of the Study:
- To assess the immunogenicity of the rhesus rotavirus vaccine MMU 18006 in infants.
- To evaluate both serum and mucosal immune responses following vaccination.
- To determine the specificity of the immune response elicited by the vaccine.
Main Methods:
- A clinical trial involving 34 children aged 3 to 20 months.
- Vaccination with varying doses of rhesus rotavirus vaccine MMU 18006.
- Immune response assessment using plaque reduction neutralization (PRN) assays and enzyme-linked immunosorbent assays (ELISA) for serum and fecal antibodies.
Main Results:
- High rate of homotypic antibody seroconversion to serotype 3 rotavirus (91%).
- Limited heterotypic antibody response to serotype 1 or 2 rotavirus.
- Detection of rotavirus-specific serum antibodies in 88% and IgA coproantibodies in 69% of vaccinated children.
Conclusions:
- Orally administered rhesus rotavirus vaccine MMU 18006 elicits local intestinal immunity.
- The vaccine primarily induces a homotypic serum neutralization response.
- The findings support the potential of MMU 18006 as a rotavirus vaccine candidate.
Abstract:
Thirty-four children 3 to 20 months of age ingested either 10(5), 10(4) or 10(3) plaque-forming units of rhesus rotavirus vaccine, MMU 18006, which possesses human rotavirus serotype 3 neutralization antigen. Immune responses were evaluated by a plaque reduction neutralization (PRN) assay to rotavirus serotypes 1, 2 and 3 and by a serum IgG, IgM and IgA and fecal IgA class-specific enzyme-linked immunosorbent assay. Homotypic PRN antibody seroconversions to serotype 3 rotavirus were detected in 31 of 34 children (91%), whereas rises in heterotypic PRN antibody to human rotavirus serotypes 1 or 2 were found in only 3 of 21 (14%) (p less than 0.00000001). Thirty of the 34 vaccinated children (88%) had at least one class of rotavirus-specific serum antibody detected by enzyme-linked immunosorbent assay. A rotavirus-specific IgA coproantibody response was seen in 11 of 16 children (69%) following vaccination. Two children who had no evidence of PRN antibody to serotype 3 after vaccination had evidence of both a fecal and a serum rotavirus-specific IgA response, suggesting that in these children the response to the vaccine was primarily mucosal. These data show that orally administered rhesus rotavirus vaccine MMU 18006 elicits local intestinal immunity but produces primarily a homotypic serum neutralization response as measured by plaque reduction neutralization assays.