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Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants
I Perez-Schael1, M Blanco, M Vilar
1Instituto de Biomedicina, Universidad Central de Venezuela, Caracas.
Insights
This Phase I trial found an oral rotavirus vaccine safe for infants, with mild reactions. While most infants developed antibodies, higher doses improved neutralization responses against common rotavirus serotypes.
Area of Science:
- Pediatrics
- Virology
- Immunology
Background:
- Rotavirus is a leading cause of severe diarrheal disease in infants globally.
- Development of safe and effective oral rotavirus vaccines is a public health priority.
- Quadrivalent vaccines offer broader protection against common rotavirus serotypes.
Purpose of the Study:
- To evaluate the safety and immunogenicity of a novel oral quadrivalent rotavirus vaccine in Venezuelan infants.
- To determine the optimal dosage for the quadrivalent rotavirus vaccine.
- To assess vaccine virus shedding in infants following oral administration.
Main Methods:
- Phase I, placebo-controlled, double-blind trial involving 130 infants aged 10-20 weeks.
- Sequential administration of three different doses of the quadrivalent rotavirus vaccine (0.25x10^4, 0.5x10^4, 10^4 PFU).
- Monitoring for adverse events, serological assays (serum IgA, plaque reduction neutralization), and stool analysis for vaccine virus shedding.
Main Results:
- The vaccine was generally safe, with only mild, transient febrile episodes observed in 15-30% of infants.
- Serum immunoglobulin A (IgA) responses ranged from 68% to 96% across dose groups.
- Neutralizing antibody responses against human rotavirus serotypes increased with dose (4-58%), while RRV neutralization was high (73-79%).
- Vaccine virus shedding occurred in all infants on lower/medium doses and 89% on the high dose, with DS1xRRV being the most frequently shed component.
Conclusions:
- The oral quadrivalent rotavirus vaccine demonstrated an acceptable safety profile in infants.
- Higher vaccine doses correlated with improved neutralizing antibody responses against key rotavirus serotypes.
- Further investigation into optimal dosing and efficacy is warranted.
Abstract:
Phase I studies of an oral quadrivalent rotavirus vaccine were conducted in 130 Venezuelan infants 10 to 20 weeks of age. The vaccine consists of a mixture of equal amounts of rhesus rotavirus (RRV) vaccine (serotype 3 [VP7]) and each of three human rotavirus-RRV reassortant strains: D x RRV (serotype 1 [VP7]), DS1 x RRV (serotype 2 [VP7]), and ST3 x RRV (serotype 4 [VP7]). Three different doses of the quadrivalent vaccine (0.25 x 10(4), 0.5 x 10(4), and 10(4) PFU of each component) were evaluated sequentially for safety and antigenicity in placebo-controlled, double-blind trials. Starting the day after vaccination, the infants were monitored by daily home visits for 7 days. Only minor reactions were observed during this period; these were limited to mild transient febrile episodes which began day 2 or 3 after vaccination and lasted 1 to 2 days in 15 to 30% of the infants. Serological studies demonstrated that 68 to 96% of the infants developed a rotavirus serum immunoglobulin A response following vaccination. However, when tested by plaque reduction neutralization assay against individual human rotavirus serotype 1, 2, 3, or 4, the response rates ranged from 4 to 23% with the low dose, 21 to 33% with the medium dose, and 32 to 58% with the high dose. Most (73 to 79%) infants developed neutralizing antibodies to RRV following administration of each dose schedule. Vaccine virus shedding was analyzed by utilizing tissue culture isolation of virus from stool. All of the infants who received the lower of medium dose and 89% of those fed the high dose shed one or more components of the vaccine. Analyses of rotavirus serotypes isolated from the stool of infants who received the 0.25 x 10(4) -PFU dose revealed that DS1 x RRV was the most commonly shed vaccine component, followed by RRV, D x RRV, and ST3 x RRV in that order.