Immunogenicity of full and fractional dose of inactivated poliovirus vaccine for use in routine immunisation and outbreak response: an open-label, randomised controlled trial.

BACKGROUND: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response. METHODS: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026. FINDINGS: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV. INTERPRETATION: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses. FUNDING: US Centers for Disease Control and Prevention.

Noninterference of Rotavirus Vaccine With Measles-Rubella Vaccine at 9 Months of Age and Improvements in Antirotavirus Immunity: A Randomized Trial.

BACKGROUND: The burden of rotavirus morbidity and mortality is high in children aged <5 years in developing countries, and evaluations indicate waning protection from rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, but coadministration of this dose should not interfere with immune responses to concurrently given vaccines. METHODS: A total of 480 9-month-old participants from Matlab, Bangladesh, were enrolled in a study with a primary objective to establish noninferiority of concomitant administration of measles-rubella vaccine (MR) and a third dose of human rotavirus vaccine (HRV; MR + HRV), compared with MR given alone. Secondary objectives included noninferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR + HRV recipients. RESULTS: Two months after vaccination, 75.3% and 74.3% of MR + HRV and MR recipients, respectively, had seroprotective levels of measles virus antibodies; 100.0% and 99.6%, respectively, showed anti-rubella virus immunoglobulin G (IgG) seroprotection. In the MR + HRV group, antirotavirus immunoglobulin A and IgG seropositivity frequencies before vaccination (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% after vaccination. CONCLUSIONS: Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases antirotavirus serum antibody titers and the proportion of infants with detectable antirotavirus antibody. CLINICAL TRIALS REGISTRATION: NCT01700621.

Considerations around the introduction of a cholera vaccine in Bangladesh.

Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a meeting on cholera and cholera vaccination in Bangladesh was convened by the Foundation Mérieux jointly with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the investment case for cholera vaccination as a complimentary control and prevention strategy. The performance of a new low cost oral cholera vaccine, Shanchol™, used in recent trials in Bangladesh, was also reviewed in the context of a potential large-scale public-sector vaccination program. Findings showed the oral vaccine to be highly cost-effective when targeting ages 1-14 y, and cost-effective when targeting ages 1+y, in high-burden/high-risk districts. Other vaccination strategies targeting urban slums and rural areas without improved water were found to be cost-effective. Regardless of cost-effectiveness (value), the budget impact (affordability) will be an important determinant of which target population and vaccination strategy is selected. Most importantly, adequate vaccine supply for the proposed vaccination programs must be addressed in the context of global efforts to establish a cholera vaccine stockpile and supply other control and prevention efforts.