Histo-Blood Group Antigen Null Phenotypes Associated With a Decreased Risk of Clinical Rotavirus Vaccine Failure Among Children <2 Years of Age Participating in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in Kenya, Mali, and the Gambia.

BACKGROUND: Previously studied risk factors for rotavirus vaccine failure have not fully explained reduced rotavirus vaccine effectiveness in low-income settings. We assessed the relationship between histo-blood group antigen (HBGA) phenotypes and clinical rotavirus vaccine failure among children <2 years of age participating in the Vaccine Impact on Diarrhea in Africa Study in 3 sub-Saharan African countries. METHODS: Saliva was collected and tested for HBGA phenotype in children who received rotavirus vaccine. The association between secretor and Lewis phenotypes and rotavirus vaccine failure was examined overall and by infecting rotavirus genotype using conditional logistic regression in 218 rotavirus-positive cases with moderate-to-severe diarrhea and 297 matched healthy controls. RESULTS: Both nonsecretor and Lewis-negative phenotypes (null phenotypes) were associated with decreased rotavirus vaccine failure across all sites (matched odds ratio, 0.30 [95% confidence interval: 0.16-0.56] or 0.39 [0.25-0.62], respectively]. A similar decrease in risk against rotavirus vaccine failure among null HBGA phenotypes was observed for cases with P[8] and P[4] infection and their matched controls. While we found no statistically significant association between null HBGA phenotypes and vaccine failure among P[6] infections, the matched odds ratio point estimate for Lewis-negative individuals was >4. CONCLUSIONS: Our study demonstrated a significant relationship between null HBGA phenotypes and decreased rotavirus vaccine failure in a population with P[8] as the most common infecting genotype. Further studies are needed in populations with a large burden of P[6] rotavirus diarrhea to understand the role of host genetics in reduced rotavirus vaccine effectiveness.

Improving adolescent human papillomavirus (HPV) immunization uptake in school-based health centers through awareness campaigns.

PURPOSE: The aim of this study was to measure the effect of a multicomponent human papillomavirus (HPV) vaccine promotion campaign on adolescent HPV vaccine uptake at school-based health centers (SBHCs) in Seattle, WA. METHODS: Youth-led HPV vaccine promotion campaigns were introduced in 2016 in 13 schools with SBHCs in Seattle. Five other schools with SBHCs served as controls. Vaccination records for students were obtained from the Washington Immunization Information System from September 2012 to August 2018. We compared increase in HPV vaccine uptake in SBHCs between 1) intervention and control schools, and 2) pre- and post-intervention periods in intervention schools using generalized estimating equations. RESULTS: HPV vaccine uptake was high at baseline among students that use SBHCs for vaccines and has steadily increased between 2012 and 2018. Implementing the promotion campaign resulted in 14% higher (95% Confidence Interval (CI): 1%, 30%) HPV vaccine uptake in intervention SBHCs compared to control SBHCs, adjusting for time and confounders. Comparing pre-and post-intervention periods in intervention SBHCs, HPV vaccine uptake was 14% higher (95% CI: -4%, 35%) in the post-intervention period. SBHCs that received more active intervention activities saw 9% higher (95% CI: 1%, 21%) vaccine uptake compared to those that received passive intervention. CONCLUSION: The vaccination promotion program implemented in a school-based setting resulted in higher HPV vaccine uptake in the post-intervention period compared to pre-intervention period, but this increase was not statistically significant. Even so, schools that received more intervention activities for longer periods of time had higher HPV vaccine uptake.

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44-64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic.