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Evaluation of a reassortant rhesus rotavirus vaccine in young children
T Tajima1, J Thompson, P F Wright
1Department of Pediatrics, Vanderbilt University, Nashville, TN 37232.
Insights
A novel live attenuated rotavirus vaccine was tested in children. Prior rotavirus exposure influenced vaccine infection rates, with seronegative children showing higher infection, and mild illness observed without gastrointestinal issues.
Area of Science:
- Virology
- Vaccinology
- Pediatrics
Background:
- Rotavirus is a leading cause of severe diarrheal disease in infants and young children worldwide.
- Development of effective rotavirus vaccines is crucial for public health.
- Live attenuated rotavirus vaccines are a key strategy for preventing rotavirus gastroenteritis.
Purpose of the Study:
- To evaluate the safety and immunogenicity of a candidate live attenuated rotavirus vaccine in children.
- To assess the impact of prior rotavirus exposure on vaccine infectivity and immune response.
- To characterize the strain specificity of the immune response elicited by the reassortant vaccine.
Main Methods:
- Oral administration of a live attenuated rotavirus vaccine (serotype 1) to 26 children.
- Vaccine derived by reassortment between rhesus rotavirus (serotype 3) and human rotavirus (serotype 1, strain Wa).
- Assessment of vaccine infectivity, immunogenicity, and safety, stratified by prior rotavirus exposure status.
Main Results:
- Vaccine infection occurred in all 14 seronegative children, but only 2 of 12 seropositive children showed reinfection.
- Mild febrile illness was observed in vaccinees, with no evidence of gastrointestinal disease.
- Serum antibody response was strain-specific against human strains but showed heterotypic neutralization against rhesus strains, suggesting antibody targeting of shared components like VP-4.
Conclusions:
- Prior rotavirus exposure significantly influences the infectivity of this candidate live attenuated rotavirus vaccine.
- The reassortant vaccine is safe, inducing mild febrile illness but no gastrointestinal symptoms.
- The vaccine elicits a protective immune response, potentially targeting conserved viral proteins like VP-4, in addition to strain-specific VP-7 immunity.
Abstract:
A candidate live attenuated rotavirus vaccine representative of serotype 1 was administered orally to 26 children, 14 of whom were undergoing primary exposure to rotavirus. The vaccine was derived by reassortment between rhesus rotavirus strain, MMU 18006, and the human serotype 1 strain Wa. The resultant virus has the gene coding for the major surface glycoprotein VP-7 from the human strain and all other genes from the attenuated rhesus parent which is a serotype 3 strain. Prior natural exposure to rotavirus determined the infectivity and immunogenicity of the vaccine. Only two of 12 seropositive children had evidence of reinfection while all 14 seronegative children were infected. Mild febrile illness was seen in vaccinees, however there was no evidence of gastrointestinal disease. As determined by neutralization of the human strains, the resultant serum antibody was entirely strain specific. However, heterotypic neutralization was seen when the rhesus strains were used, suggesting that neutralizing antibody can be directed to shared components of the donor and reassortant strain presumably VP-4, the other major surface protein.