Research in context

Pneumococcal conjugate vaccines (PCVs) have been available since 2000, but an estimated 60% of the world's children are unvaccinated. Vaccination strategies providing greater accessibility and affordability are urgently needed. Reduced-dose schedules offer one such strategy. A single dose at or after 12 months of age (0 + 1 schedule) might be enough for the maintenance of herd protection, and the addition of a dose in infancy (1 + 1 schedule) would enhance the response to that dose and provide some protection during the first year of life. We searched PubMed from database inception to Oct 19, 2022, using search terms including but not limited to “pneumococcal conjugate vaccine”, “schedule”, “reduced-dose”, “immunogenicity”, and “carriage”. Two trials, from the UK and South Africa, have compared the immunogenicity of 1 + 1 and 2 + 1 PCV schedules (PCV13 in the UK and both PCV10 and PCV13 in South Africa). Both trials found that post-booster responses with the 1 + 1 schedules were similar to those with the 2+ 1 schedules for most serotypes. Neither trial evaluated the effects on nasopharyngeal carriage. Our previous trial in Ho Chi Minh City, Viet Nam, showed that a 1 + 1 PCV10 schedule administered at 2 months and 6 months of age was immunogenic and reduced nasopharyngeal carriage of vaccine serotypes at 18 months by 40%. We also showed that a single dose of PCV10 administered at 18 months of age was immunogenic and reduced vaccine-type carriage at 24 months by 60%. In Kenya, a 0 + 1 PCV10 schedule at 12–59 months was also shown to be immunogenic and reduced vaccine-type carriage by 47% 2 months later and by 29% 4 months later.
To our knowledge, this is the first trial to evaluate 0 + 1 and 1 + 1 PCV schedules concurrently. The trial also incorporates a head-to-head comparison of PCV10 and PCV13 in each schedule. The primary outcome measure is vaccine-type carriage and the trial includes an unvaccinated control group, enabling estimation of the vaccine efficacy against carriage during the first 2 years of life. We show that 0 + 1 and 1 + 1 schedules of PCV10 or PCV13 all reduce carriage of vaccine serotypes during the second year of life, with a greater effect generally seen with the 1 + 1 than the 0 + 1 schedules. Such data are crucial as they provide a proxy measure for the reduction in transmission to unvaccinated individuals and therefore the probable herd protection effects of the different schedules. This trial also evaluates the immunogenicity of the different schedules, both in terms of serotype-specific IgG and functional antibody levels by opsonophagocytic assay to all serotypes in PCV10 and PCV13. A dose of PCV in infancy elicits stronger immune responses with PCV10 than PCV13, and a dose at 12 months of age elicits stronger responses with PCV13 than PCV10. With both vaccines, responses to the 12-month dose are significantly enhanced by provision of a priming dose in infancy.
This trial adds substantially to the small body of pre-existing evidence supporting the use of reduced-dose PCV schedules. Consistent with previously published findings, data from our trial show that both 1 + 1 and 0+1 schedules of PCV10 and PCV13 reduce vaccine-type carriage and are immunogenic. With both vaccines, a 1 + 1 schedule has a greater effect on carriage and generates stronger immune responses than a 0 + 1 schedule. PCV10 is more immunogenic as a primary dose, whereas PCV13 is more immunogenic as a booster. A mixed-regimen 1 + 1 schedule with a primary dose of PCV10 and a booster dose of PCV13 warrants investigation. 1 + 1 schedules should be considered for countries with mature PCV programmes where herd protection has been established and for countries considering PCV introduction in conjunction with a comprehensive catch-up campaign. Immunogenicity and efficacy against carriage of 0 + 1 schedules support single-dose administration in humanitarian crises and remote settings where access to PCV is challenging.