Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons : a randomized, double-blind, placebo-controlled trail

BACKGROUND: Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Conficence interval: 56% to 88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against server RGVE over two consecutive rotavirus seasons in South African children. METHODS: A prospective, double-blind, placebo controlled multi-centered trail in South Afria and Malawi randomly assigned infants in a 1:1:1 ration to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale. RESULTS: 1,339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1,035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1 to 83). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects. CONCLUSION: Rotarix is associated with significant reductions in servere gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children.GAVI Alliance and GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium.http://www.elsevier.com/locate/vaccin

Modeling the long-term persistence of neutralizing antibody in children and toddlers after vaccination with live attenuated Japanese encephalitis chimeric virus vaccine

The live-attenuated Japanese encephalitis chimeric virus vaccine JE-CV (IMOJEV®, Sanofi Pasteur) elicits a robust antibody response in children, which wanes over time. Clinical efficacy is based on a correlate of protection against JE infection defined as neutralizing antibody levels equal to or greater than the threshold of 10 (1/dil). Information on the duration of persistence of the JE antibody response above this threshold is needed. We constructed statistical models using 5-year persistence data from a randomised clinical trial (NCT00621764) in children (2–5 years old) primed with inactivated JE vaccine who received a booster dose of JE-CV, and in JE-naïve toddlers (12–24 months) who received a JE-CV single dose primary vaccination. Models were constructed using a Bayesian Monte-Carlo Markov Chain approach and implemented with OpenBugs V3.2.1. Antibody persistence was predicted for up to 10 years following JE-CV vaccination. Findings from a piecewise model with 2 phases (children) and a classic linear model (toddlers) are presented. For children, predicted median antibody titers (77 [2.5th–97.5th percentile range 41–144] 1/dil) remained above the threshold for seroprotection over the 10 years following booster JE-CV vaccination; the predicted median duration of protection was 19.5 years. For toddlers, 10 years after JE-CV primary vaccination median antibody titers were predicted to wane to around the level required for seroprotection (10.8 [5.8–20.1] 1/dil). A booster dose of JE-CV in children is predicted to provide long-term protection against JE. Such data are useful to facilitate decisions on implementation of and recommendations for future vaccination strategies

Immunogenicity and safety of a dengue vaccine given as a booster in Singapore: a randomized Phase II, placebo-controlled trial evaluating its effects 5?6 years after completion of the primary series

10.1080/21645515.2019.1661204Human Vaccines & Immunotherapeutics163523-52

Immunogenicity and safety of a dengue vaccine given as a booster in Singapore: a randomized Phase II, placebo-controlled trial evaluating its effects 5–6 years after completion of the primary series

The tetravalent dengue vaccine (CYD-TDV; Dengvaxia®) is administered on a three-dose schedule, 6 months apart in those aged ≥9 years in a number of dengue-endemic countries in Asia and Latin America. In this study, CYD63 (NCT02824198), participants aged 9–45 years at first vaccination, and who had received three doses of CYD-TDV in the CYD28 study more than 5 years previously, were randomized 3:1 to receive a booster CYD-TDV dose (Group 1) or placebo (Group 2). Dengue neutralizing antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were assessed in sera collected before and 28 days after booster injections. Non-inferiority of the booster immune response versus that induced after the third dose was demonstrated for each serotype if the lower limit of the two-sided 95% confidence interval (CI) was >0.5 for the GMT ratios (GMTRs) between post-booster CYD-TDV dose and post-dose 3 in Group 1. Overall, 118 participants received CYD-TDV booster or placebo and 116 (98.3%) completed the study; two participants were withdrawn because of noncompliance. GMTs in the booster CYD-TDV group increased across all serotypes post-booster injection by 1.74- (serotype 1) to 3.58-fold (serotype 4). No discernible increases were observed in the placebo group. Non-inferiority was demonstrated for serotypes 1, 3, and 4, but not for serotype 2 (GMTR; 0.603 [95% CI, 0.439– 0.829]). No safety issues were observed. These data show that the CYD-TDV booster given 5 or more years later tended to restore GMTs back to levels observed post-dose 3

Safety and immunogenicity of Clostridium difficile toxoid vaccine in Japanese adults

This was a randomized, placebo-controlled, Phase I/II study conducted in a Japanese cohort to assess the safety and immunogenicity of Clostridium difficile vaccine (the same formulation as that used in the ongoing global Phase III study). Healthy Japanese adults aged 40–75 years were randomized to receive either C. difficile vaccine (N = 67) or placebo (N = 34) by intramuscular injection on Days 0, 7, and 30. Serum IgG specific for toxins A and B was measured by enzyme-linked immunosorbent assay (ELISA) and in vitro functional activity by toxin neutralizing assay (TNA). The seroconversion rate (percentage of participants with a ≥4-fold rise in antibody levels from baseline) was high for both toxin A (ELISA and TNA) and toxin B (ELISA), approaching 100% for each by Day 60. For toxin B assessed by TNA, however, the response was lower, with the seroconversion rate not rising significantly beyond the value of 42.9% seen on Day 14 (44.4% at Day 60). Although the response in the participants who were seronegative at baseline was slower than that in those who were seropositive, seroconversion was seen in nearly all (100%) subjects by Day 60, with the exception of the response to toxin B evaluated using TNA (16–18% on Days 14–60). The proportion of participants with solicited local reactions, solicited systemic reactions, and vaccine-related unsolicited reactions were 67.6%, 19.1%, and 20.6%, respectively. Most of the adverse reactions were mild to moderate in intensity, occurring within 3 days post-vaccination, and resolving by 3–6 days post-vaccination. There were no withdrawals due to adverse events and no serious adverse events. These data confirm the safety and immunogenicity of C. difficile vaccine in Japanese adults

Efficacy of human rotavirus vaccine RIX4414 in malnourished children

Ministerio de Salud. Universidad Central de Venezuela. Instituto de Biomedicina. Caracas, VE.Universidad de Carabobo. Insalud. Ciudad Hospitalaria “Dr. Enrique Tejera". Valencia, VE.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Ciudad México, México.Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Ciudad México, México.GlaxoSmithKline Biologicals. Rixensart, Belgium.GlaxoSmithKline Biologicals. Rixensart, Belgium.The effect of nutritional status on protective efficacy of a live attenuated human rotavirus vaccine (RIX4414) was studied. Vaccine protection was evaluated through a secondary analysis of data from an efficacy study conducted in Brazil, Mexico, and Venezuela. Vaccine efficacy against rotavirus gastroenteritis (RVGE) was similar in well-nourished and malnourished infants: 74.1 percent (95 percent confidence interval [CI], 52.2 percentû86.2 percent) and 73 percent (95 percent CI, 11.2 percentû92.3 percent) for severe RVGE and 60.9 percent (95 percent CI, 37.4 percentû75.4 percent) and 61.2 percent (95 percent CI, 10.4 percentû83.1 percent) for RVGE of any severity, respectively. RIX4414 significantly decreased the rate of RVGE regardless of nutritional status, which suggests that this patient group can also benefit from rotavirus vaccination

Long-term immunogenicity and safety of tetravalent dengue vaccine (CYD-TDV) in healthy populations in Singapore and Vietnam: 4-year follow-up of randomized, controlled, Phase II trials

10.1080/21645515.2019.1578595Human Vaccines & Immunotherapeutics15102315-232