A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children.

We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P [8] 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.

[Genetic variation in VP7 gene of rotavirus serotype G3 predominated in Changchun, China].

Group A rotavirus (RV) is the most important etiologic agent of severe gastroenteritis among children and the development of an effective vaccine becomes the top public health priority. Since survey of RV serotypes circulating in local community is important for introduction or development of RV vaccine, RV serotype G3 had proved as the predominant strain in Changchun from 2001 to 2005. Stool specimens collected from children with acute diarrhea were tested for group A rotavirus by enzyme-linked immunosorbent assay (ELISA) and RV isolates were typed by reverse transcription-polymerase chain reaction (RT-PCR) using serotype-specific primers. The complete VP7 gene segments of 31 rotavirus strains selected in Changchun from 1999 to 2005 were amplified with RT-PCR. Amplicons were cloned and sequenced. Comparative analysis of the VP7 sequences showed that there were no obvious differences among 31 RV strains. There was similar genetic variation among VP7 genes during the same RV season. The nucleotide sequence of VP7 gene of six G3 RV strains had one base deletion at nt1038 in 2003 RV season. The nucleotide mutations in regions A, B and C of VP7 gene took place at the same position or position near-by. Increase of nucleotide mutation in non- high variation region may benefit maintenance of serotype G3 as pre dominant strain after 2002. Increase of non continuous variation in non-high variation regions was notable.