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• Oral rotavirus vaccines underperform in low-income countries. • A double vaccine dose did not improve immune response among infants in Bangladesh. • Infants with vaccine replication had improved antibody responses. • Interventions to improve gut health and promote vaccine replication are needed. Oral, live-attenuated rotavirus vaccines suffer from impaired immunogenicity and efficacy in low-income countries. Increasing the inoculum of vaccine might improve vaccine response, but this approach has been inadequately explored in low-income countries. We performed a double-blind, parallel group, randomized controlled trial from June 2017 through June 2018 in the urban Mirpur slum of Dhaka, Bangladesh to compare vaccine take (primary outcome) among healthy infants randomized to receive either the standard dose or double the standard dose of oral Rotarix (GlaxoSmithKline) vaccine at 6 and 10 weeks of life. Infants with congenital malformations, birth or enrollment weight <2000 gm, known immunocompromising condition, enrollment in another vaccine trial, or other household member enrolled in the study were excluded. Infants were randomized using random permuted blocks. Vaccine take was defined as detection of post-vaccination fecal vaccine shedding by real-time reverse transcription polymerase chain reaction with sequence confirmation or plasma rotavirus-specific immunoglobulin A (RV-IgA) seroconversion 4 weeks following the second dose. 220 infants were enrolled and randomized (110 per group). 97 standard-dose and 92 high-dose infants completed the study per-protocol. For the primary outcome, no significant difference was observed between groups: vaccine take occurred in 62 (67%) high-dose infants versus 69 (71%) standard-dose infants (RR 0.92, 95% CI 0.67–1.24). However, in post-hoc analysis, children with confirmed vaccine replication had significantly increased RV-IgA responses, independent of the intervention. No significant adverse events related to study participation were detected. Administration of double the standard dose of an oral, live-attenuated rotavirus vaccine (Rotarix) did not improve vaccine take among infants in urban Dhaka, Bangladesh. However, improved immunogenicity in children with vaccine replication irrespective of initial inoculum provides further evidence for the need to promote in-host replication and improved gut health to improve oral vaccine response in low-income settings. ClinicalTrials.gov: NCT02992197. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Between July 2002 and April 2003, over 21000 individuals were revaccinated against smallpox by the Israeli Ministry of Health. The objectives of the campaign were to create an immunized core of first responders, to review vaccination techniques, and to produce vaccinia immune globulin (VIG). Methods: The Lister strain of vaccinia virus was used at a concentration of approximately 107 pock-forming units (PFU)/ml, and was administered by the multiple-puncture technique. The revaccinees were from varied ethnic backgrounds, almost all were aged 25–64 years, and all participants had been vaccinated against smallpox in the past. Results: The proportion of clinical take was 66.1% (95% CI: 65.2%, 67.0%), similar to past vaccination programs when take also occurred in approximately two thirds of vaccinees. An antibody response occurred in 77.7% (95% CI: 74.8%, 80.6%) of all revaccinees: 94.4% (95% CI: 91.8%, 96.3%) of those with clinical take and 56.6% (95% CI: 51.3%, 61.8%) of those without clinical take. The most common side effects corresponded to symptoms of non-specific viral diseases, and only a few revaccinees reported serious side effects. Conclusions: The campaign achieved all its basic goals and provided useful lessons for any mass-vaccination programs that might be necessary in the future. [Copyright &y& Elsevier]