In a study recently published in The Lancet, 3 new aluminum hydroxide adjuvanted, reduced-dose, inactivated polio vaccines (IPV-Al) developed by AJ Vaccines A/S (Denmark) were found to exhibit safety and efficacy profiles comparable to the standard comparator inactivated polio vaccine (IPV).
“Clinical trial results showed that all 3 formulations of low dose IPV with aluminum were noninferior compared to the presently approved IPV vaccine in the tested vaccination schedule,” said Niels Thulstrup, vice president, business development at AJ Vaccines A/S, Copenhagen, Denmark, in an email interview with Infectious Disease Advisor. “Furthermore, the study showed that the vaccines were well tolerated.”
The phase 2, non-inferiority, observer-blinded, parallel, randomized, controlled dose trial (ClinicalTrials.gov identifier: NCT02347423) was conducted at Hospital Maternidad Nuestra Señora de la Altagracia in Santo Domingo, Dominican Republic, and enrolled 824 healthy 6-week-old infants between February 2, 2015, and September 26, 2015. Study participants were allocated to 1 of 4 study groups; 3 groups received the investigational reduced-dose IPV-Al vaccines and 1 group received the IPV comparator vaccine.
All 3 investigational IPV-Al vaccines contained the same inactivated poliovirus strains as the comparator IPV —type 1 (Brunhilde), type 2 (MEF-1), and type 3 (Saukett) strains — in reduced-dose ratios (1/3 IPV-Al, 1/5 IPV-Al, and 1/10 IPV-Al). Vaccinations were performed according to the Expanded Programme on Immunization (EPI) schedule at visits 1, 2, and 3, which corresponded to the infants’ age of 6 weeks, 10 weeks, and 14 weeks, respectively. Blood samples were collected 3 times throughout the course of the study: at age 6 weeks (visit 1), 14 weeks (visit 3,) and 18 weeks (visit 4).
The lower 2-sided 90% CIs of seroconversion rate differences were greater than -10% for all 3 poliovirus types, confirming non-inferior immunogenicity of all 3 investigational IPV-Al vaccines. Furthermore, after the third vaccination, seroconversion for poliovirus types 1 and 3 was induced in more than 98% of infants for all 3 reduced-dose IPV-Al vaccines. Upon completion of the EPI schedule, the seroconversion rates for 1/10 IPV-Al vaccine, which contained only one-tenth of a standard dose of IPV, were 99%, 95%, and 100% for types 1, 2, and 3 poliovirus, respectively. Reported adverse events (AEs) included mild reactions at the injection site (3) and systemic AEs (16). In addition, 3 serious AEs unrelated to the vaccinations were also observed.
“Based upon the results of the phase 2 clinical trial, it was decided to bring the 1/10 dose forward into phase 3 clinical trials,” explained Thulstrup. “These trials are presently recruiting in Panama and the Philippines; a positive outcome of the trials will be used to obtain WHO [World Health Organization] prequalification for the product.”
Thulstrup is optimistic about the potential use of the reduced-dose IPV-Al vaccine in the global fight against polio. He believes that it “will provide a low-cost alternative to the presently used IPV vaccines.” In addition, he expects that the reduced antigen dose used in the vaccine will make polio vaccination more accessible, thereby facilitating polio eradication efforts.
Rivera L, Pedersen RS, Peña L, et al. Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomized, and controlled dose investigational trial [published online April 25, 2017]. The Lancet. doi:10.1016/S1473-3099(17)30177-9