A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children
The National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam. Vaccine
(Impact Factor: 3.62).
04/2012; 30 Suppl 1(Suppl 1):A114-21. DOI: 10.1016/j.vaccine.2011.07.118
We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P  strain (KH0118-2003) isolated from a child in Vietnam. The vaccine was tested first for safety in 29 healthy adults. When deemed safe, it was further tested for safety and immunogenicity in 160 infants (4 groups) aged 6-12 weeks in a dose and schedule ranging study. The vaccine was administered in low titer (10(6.0)FFU/dose) on a 2-dose schedule given 2 months apart (Group 2L) and on a 3-dose schedule given 1 month apart (Group 3L) and in high titer (10(6.3)FFU/dose) in 2 doses 2 months apart (Group 2H) and in 3 doses 1 month apart (Group 3H). For comparison, 40 children (group Rotarix™) were given 2 doses of the lyophilized Rotarix™ vaccine (10(6.5)CCID(50)/dose) 1 month apart. All infants were followed for 30 days after each dose for clinical adverse events including diarrhea, vomiting, fever, abdominal pain, irritability and intussusception. Immunogenicity was assessed by IgA seroconversion and viral shedding was monitored for 7 days after administration of each dose. Two doses of Rotavin-M1 (10(6.3)FFU/dose) were well tolerated in adults. Among infants (average 8 weeks of age at enrollment), administration of Rotavin-M1 was safe and did not lead to an increased rate of fever, diarrhea, vomiting or irritability compared to Rotarix™, indicating that the candidate vaccine virus had been fully attenuated by serial passages. No elevation of levels of serum transaminase, blood urea, or blood cell counts were observed. The highest rotavirus IgA seroconversion rate (73%, 95%CI (58-88%)) was achieved in group 2H (2 doses--10(6.3)FFU/dose, 2 months apart). The 2 dose schedules performed slightly better than the 3 dose schedules and the higher titer doses performed slightly better than the lower titer doses. These rates of seroconversion were similar to that of the Rotarix™ group (58%, 95%CI (42-73%)). However more infants who received Rotarix™ (65%) shed virus in their stool after the first dose than those who received Rotavin-M1 (44-48%) (p<0.05) and the percent shedding decreased after subsequent doses of either vaccine. Rotavin-M1 vaccine is safe and immunogenic in Vietnamese infants. A trial in progress will assess the safety, immunogenicity and efficacy of Rotavin-M1 (2 doses at 10(6.3)FFU/dose) in a larger number of infants. The trial registration numbers are NCT01375907 and NCT01377571.
Available from: Daniel E Velasquez
- "Despite temporal and geographic variations of strains, both vaccines have showed sustained reduction of severe diarrheal disease in infants and young children since their introduction in some countries (Cortes et al., 2011; Gastanaduy et al., 2013). At the same time, these results give increased confidence with respect to other monovalent rotavirus vaccines in clinical development, including the recently licensed Rotavac Ò vaccine in India and Rotavin in Vietnam, (Dang et al., 2012) and the Australian RV3-BB vaccine (Danchin et al., 2013) (all Wa-like constellation). Despite the vast diversity in G/P-genotype combinations, rotavirus A strains causing widespread severe gastroenteritis in humans belong to a Wa-like or DS-1-like genotype constellation (Matthijnssens and Van Ranst, 2012). "
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ABSTRACT: While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P and the fully heterotypic G2P strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines.
Available from: Roger I Glass
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ABSTRACT: Tenth International Rotavirus Symposium Bangkok, Thailand, 19-21 September 2012 Over 350 scientific, public and private sector experts from 47 countries convened at the Tenth International Rotavirus Symposium in Bangkok, Thailand on 19-21 September 2012 to discuss progress in the prevention and control of rotavirus, the leading cause of diarrhea hospitalizations and deaths among young children worldwide. Participants discussed data on the burden and epidemiology of rotavirus disease, results of trials of rotavirus vaccines, postmarketing data on vaccine impact and safety from countries that have implemented rotavirus vaccination programs, new insights in rotavirus pathogenesis, immunity and strain diversity, and key issues related to vaccine policy and introduction.
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