Fractional dosing of pneumococcal conjugate vaccine noninferior to full dosing schedule
1. In this randomized non-inferiority trial, 40% of a full dose of the 13-valent pneumococcal conjugate vaccine (PCV13) was noninferior to the full doses for all included serotypes.
2. Lower doses of the PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10) did not meet criteria for noninferiority.
Evidence Rating Level: 2 (Good)
Study Rundown: The pneumococcal conjugate vaccine is highly effective at reducing vaccine-type pneumococcal disease. This vaccine has been introduced as part of routine recommended vaccinations globally. However, it is currently the most expensive component of routine immunization schedules in many countries. Currently, the vaccine is given in a three prime – no booster series of doses or a two prime – one booster schedule. The sustainability of this vaccine program is in question in countries that are transitioning out of financial support. Fractional doses of antigens have been shown to induce immune responses that are noninferior to the current full-dose vaccines in a variety of different diseases. This randomized noninferior trial aimed to assess whether the serotype-specific immunogenicity of fractional doses (20% or 40%) of PCV10 or PCV13, administered in a two prime – one booster schedule, would be noninferior to the immunogenicity of the current full doses. The prevalence of vaccine serotype carriage was also assessed. Infants that met the inclusion criteria were randomly assigned to one of seven groups, where groups A through F were assigned to receive either a fractional or full dose of PCV10 or PCV13, administered as two primary doses plus one booster. Participants in group G received a full dose of PCV10 as three primary doses without a booster. Results from this study found that in a three-dose schedule, 40% of doses of the PCV13 were noninferior to the full doses in all serotypes. However, lower doses of PCV13 and PCV10 did not meet noninferiority.
Click here to read the study in NEJM
In-Depth [randomized noninferiority trial]: This randomized noninferior trial assessed whether the immunogenicity of PCV10 and PCV13 would be noninferior to the full doses. The prevalence of vaccine serotype carriage was also assessed. Healthy infants in Kilifi and Mombasa counties in Kenya were randomly assigned to one of seven trial groups when they were six to eight weeks of age and received follow-up until 18 months of age. Participants in groups A through F were assigned to receive either a fractional or full dose of PCV10 or PCV13, administered as two primary doses plus one booster. In group A, participants received a full dose of PCV13; group B, a 40% dose of PCV13; group C, a 20% dose of PCV13; group D, a full dose of PCV10; group E, a 40% dose of PCV10; and group F, a 20% dose of PCV10. Participants in group G received a full dose of PCV10 as three primary doses without a booster. Immunogenicity was then assessed four weeks after the primary series of doses and four weeks after the booster. Noninferiority was declared if the difference in threshold response was ≤10% after the primary series, or if the GMC ratio of IgG was >0.5 after the booster. A dose was considered noninferior if it met the criterion for ≥8 of 10 PCV10 serotypes or ≥10 of 13 PCV13 serotypes; carriage was assessed at six and 18 months. The results from this study found that in a two-prime – one booster schedule, a 40% dose of the PCV13 was noninferior to the full dose for IgG responses in all serotypes. However, when PCV13 and PCV10 were administered in lower doses (20%), the immunogenicity was not noninferior to the full dose. The prevalence of vaccine serotype carriage was similar across all PCV13 groups when the participants were 9 to 18 months of age. In summary, fractional dosing of PCV13 was noninferior to full dosing for all studied serotypes.
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