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Bash M.C.,Center for Biologics Evaluation and Research | Lynn F.,Center for Biologics Evaluation and Research | Mocca B.,Center for Biologics Evaluation and Research | Borrow R.,Public Health England | And 8 more authors.
Clinical and Vaccine Immunology | Year: 2014

A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC′) was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC′ and then used the SBA assay with hC′ (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12- to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC′ lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC′. hSBA titers determined using three independent lots of pooled hC′ were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC′ is feasible and showed that PsA-TT was highly immunogenic in African toddlers. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Breiman R.F.,Centers for Disease Control and Prevention | Zaman K.,International Center for Diarrheal Disease Research | Armah G.,University of Ghana | Sow S.O.,Center Pour le Developpement des Vaccins | And 7 more authors.
Vaccine | Year: 2012

Background: Efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq®, against severe rotavirus gastroenteritis (RVGE) was evaluated in two double-blind, placebo-controlled, multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa (Ghana, Kenya, and Mali) and in Asia (Bangladesh and Vietnam) from March 2007 through March 2009. The findings from each continent have been analyzed and presented separately, according to a single identical protocol. Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV. Methods: 6674 infants (4705 infants from Africa and 1969 infants from Asia), randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age according to each country's EPI schedule, were included in the per protocol efficacy analysis. Breastfeeding and concomitant administration of EPI vaccines, including OPV, were allowed. Episodes of gastroenteritis (GE) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale. Stool samples were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes. We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points (score ≥ 11, severe; score ≥ 15, very severe). Results: Vaccine efficacy (VE) against RVGE, regardless of serotype, through the entire follow-up period for any severity, severe (score ≥ 11), and very severe (score ≥ 15) was 33.9%, 95% CI (22.7, 43.5), 42.5%, 95% CI (27.4, 54.6), and 51.2%, 95% CI (26.3, 68.2), respectively. Through the first year of life, VE against severe RVGE was 58.9%, 95% CI (40.0, 72.3) and against all-cause severe GE was 23.0%, 95% CI (5.4, 37.3). VE against severe RVGE caused by non-vaccine G serotypes, G8 and G9, through the entire follow-up period was 87.5%, 95% CI (6.8, 99.7) and 48.0%, 95% CI (-5.5, 75.6), respectively. All G8 strains were associated with P2A[6] (a P-type not contained in PRV), while the majority of the G9 strains were associated with P1A[8] (a P-type contained in PRV). Conclusions: Combining data from the 5 sites strengthens the precision of VE estimates and reveals rising VE with increased RVGE severity. Extrapolating data from VE against severe GE and RVGE suggest that 39% of severe GE episodes during the first year of life were due to rotavirus, highlighting substantial, potentially preventable, public health burden of RVGE. PRV provides protection against non-vaccine serotypes (G8P2A[6]). © 2011.

Tracy L.,University of Maryland College Park | Gaff H.D.,Old Dominion University | Burgess C.,Mathematics Ecology | Sow S.,University of Maryland College Park | And 3 more authors.
Clinical Infectious Diseases | Year: 2011

Human papillomavirus vaccines have potential to reduce cervical cancer incidence and mortality; however, cultural and economic barriers may hinder success in developing countries. We assessed impact of a single vaccine campaign in Mali with use of mathematical modeling. Our model shows that decreases in the prevalence of Human papillomavirus infection are proportional to achieved vaccination coverage. © The Author 2011.

Tracy J.K.,University of Maryland Baltimore County | Schluterman N.H.,University of Maryland Baltimore County | Greene C.,University of Maryland Baltimore County | Sow S.O.,University of Maryland Baltimore County | And 2 more authors.
Vaccine | Year: 2014

Background: Human papillomavirus (HPV) vaccines have the potential to reduce cervical cancer incidence and mortality, particularly in the parts of the developing world that bear the greatest burden of disease. This research sought to predict the impact and cost-effectiveness of an HPV vaccination program in an example low-resource country with a high burden of cervical cancer: Mali, West Africa. Methods: Novel compartmental mathematical models projected the impact of adolescent HPV vaccination in urban and rural areas of Mali. The models accounted for two high-risk vaccine-types: HPV 16 and 18. We then attached comprehensive real cost and cost-effectiveness estimates. Results: Our models predict that HPV vaccination in Mali will reduce cervical cancer burden by a factor roughly equal to vaccine coverage. A point vaccination program was simulated in a cohort of 333,146 urban and 588,982 rural Malian women, age 10-14. Vaccination of 50% of girls reduced the peak prevalence of HPV 16/18 to 5.0% in the urban setting and 9.6% in the rural setting, down from 11.7% and 22.0%, respectively, with no vaccination. The 50% vaccination scenario averted 1145 cervical cancer deaths in the urban group and 2742 in the rural group. The cost per discounted life-year saved in this scenario was 1030 US dollars (urban) and 725 dollars (rural). The cost per life-year saved was higher at 90% coverage, but was still in the range of a "cost-effective" public health intervention. Conclusions: This research yielded the most comprehensive real cost estimates of HPV vaccination yet published for sub-Saharan Africa. Our models indicate that HPV vaccination in Mali will be cost-effective when introduced. To maximize the benefit using limited resources, vaccination programs may begin with a target coverage of about 50%. We anticipate that costs of reaching late adopters after the First Vaccinated Wave of vaccination will be higher, but worthwhile. © 2014 Elsevier Ltd.

Sow S.O.,Center Pour le Developpement des Vaccins | Tapia M.,Center Pour le Developpement des Vaccins | Tapia M.,University of Maryland Baltimore County | Haidara F.C.,Center Pour le Developpement des Vaccins | And 16 more authors.
Vaccine | Year: 2012

The oral, pentavalent rotavirus vaccine (PRV), RotaTeq was assessed for prevention of severe rotavirus gastroenteritis (RVGE) in young children in two multi-site, randomized, placebo-controlled field trials; one in Asia (Vietnam and Bangladesh) and the other in sub-Saharan Africa (Ghana, Kenya and Mali). The efficacy results for the Mali site of the multi-country trial are presented here. We randomly assigned infants in a 1:1 ratio to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. Gastroenteritis episodes were captured passively at the local health centers and by home visits. The primary study outcome was severe RVGE, as defined by a score of ≥11 using the Vesikari Clinical Scoring System occurring ≥14 days after the third dose until the end of the study. Other efficacy analyses included efficacy against severe RVGE through the first year and during the second years of life, as well as efficacy after receiving at least one dose of vaccine. In total, 1960 infants were enrolled in the trial at the Mali site and sera were collected on a subset of infants (approximately 150) for immunogenicity testing. In the first year of follow-up, largely due to cultural practices to visit traditional healers as the first point of care, the point estimate of efficacy was unreliable: the per protocol vaccine efficacy against severe RVGE was 1% (95% confidence interval [CI]: -431.7, 81.6); the intention-to-treat vaccine efficacy was 42.9% (95% CI: -125.7, 87.7). During the second year of follow-up, after the surveillance system was modified to adapt to local customs and health care seeking practices, the point estimate of per-protocol vaccine efficacy was 19.2% (95% CI: -23.1,47.3%). 82.5% of Malian infants (95% CI: 70.1,91.3%) who received PRV mounted a seroresponse (≥3-fold rise from baseline (prevaccination) to post-dose 3 vaccination) of anti-rotavirus immunoglobulin A antibody, with a post third-dose geometric mean titer (GMT) of 31.3. units/mL. By contrast, only 20.0% of placebo recipients (95% CI: 10.0, 33.7%) developed a seroresponse and the post-third dose GMT was 3.2. units/mL. None of the serious clinical adverse events observed were considered to be vaccine-related. © 2011 Elsevier Ltd.

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