英国伦敦卫生和热带医学院Katherine E. Gallagher团队研究了肺炎球菌结合疫苗部分剂量接种的有效性。该研究于2024年9月26日发表于《新英格兰医学杂志》。

肺炎球菌结合疫苗是常规免疫计划中昂贵的组成部分。部分剂量方案可能是提高疫苗计划可持续性的一种选择。

研究组评估了10价和13价肺炎球菌结合疫苗（分别为PCV10[GSK]和PCV13[辉瑞]）的部分剂量免疫原性是否不劣于全剂量，并分析了疫苗血清型携带的流行率。他们将肯尼亚的健康婴儿随机分配到七个同等规模的试验组中。A至F组的参与者被分配接受PCV10或PCV13的部分或全部剂量，分为两次主剂量加一次加强剂量。在A组中，参与者接受了全剂量的PCV13；B组，40%剂量的PCV13；C组，20%剂量的PCV13；D组，全剂量PCV10；E组，40%剂量的PCV10；F组为20%剂量的PCV10。第七组（G组）的参与者在没有加强针的情况下接受了全剂量PCV10的三次主剂量。

在初次系列给药后4周和加强剂给药4周后评估免疫原性。如果具有阈值反应的参与者百分比的差异不超过10%，则可以在初次系列试验后4周宣布非劣效性，如果IgG的几何平均浓度（GMC）比超过0.5，则在加强针给药后4周可以宣布非劣效性。如果疫苗剂量符合PCV10组中10种疫苗类型中至少8种或PCV13组13种疫苗类型的至少10种的非劣效标准，则该疫苗剂量被预先指定为非劣效。参与者在9个月和18个月大时进行了血清携带状态的评估。

在按方案分析中，40%的全剂量PCV13在初级系列给药后符合13种血清型中的12种的非劣效性标准，在加强针后符合13种血清型中13种的非劣效性标准。20%剂量PCV13及40%、20%剂量PCV10的免疫原性并不劣于全剂量。在9个月龄和18个月龄时，PCV13组的疫苗血清型携带率相似。

研究结果表明，在三剂计划中（两剂主剂量和一剂加强剂），对于所有纳入的血清型，40%的PCV13剂量均不劣于全剂量。低剂量的PCV13和PCV10不符合非劣效性标准。

附：英文原文

Title: Fractional Doses of Pneumococcal Conjugate Vaccine — A Noninferiority Trial

Author: Katherine E. Gallagher, Ruth Lucinde, Christian Bottomley, Mary Kaniu, Badaud Suaad, Mary Mutahi, Laura Mwalekwa, Sarah Ragab, Louise Twi-Yeboah, James A. Berkley, Mainga Hamaluba, Angela Karani, Jimmy Shangala, Mark Otiende, Elizabeth Gardiner, Daisy Mugo, Peter G. Smith, Collins Tabu, Fred Were, David Goldblatt, J. Anthony G. Scott

Issue&Volume: 2024-09-26

Abstract:

BACKGROUND

Pneumococcal conjugate vaccines are an expensive component of the routine immunization schedule. Fractional-dose regimens may be one option to increase the sustainability of the vaccine program.

METHODS

We assessed whether the immunogenicity of fractional doses of the 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10 [GSK] and PCV13 [Pfizer], respectively) would be noninferior to that of the full doses and analyzed the prevalence of vaccine-serotype carriage. We randomly assigned healthy infants in Kenya to one of seven equal-sized trial groups. 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 dose. 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 the seventh group (group G) received a full dose of PCV10 as three primary doses without a booster. Immunogenicity was assessed 4 weeks after the primary series of doses and 4 weeks after the booster dose. Noninferiority could be declared 4 weeks after the primary series if the difference in the percentage of participants with a threshold response was not more than 10% and 4 weeks after administration of the booster if the ratio of the geometric mean concentration (GMC) of IgG was more than 0.5. A vaccine dose was prespecified as noninferior if it met the noninferiority criterion for at least 8 of the 10 vaccine types in the PCV10 groups or at least 10 of the 13 vaccine types in the PCV13 groups. Carriage was assessed when participants were 9 months and 18 months of age.

RESULTS

In the per-protocol analysis, 40% of a full dose of PCV13 met the noninferiority criterion for 12 of 13 serotypes after the primary series and for 13 of 13 serotypes after the booster. The immunogenicity of the 20% dose of PCV13 and of the 40% and 20% doses of PCV10 was not noninferior to that of the full doses. Vaccine serotype-type carriage prevalence was similar across the PCV13 groups at 9 months and 18 months of age.

CONCLUSIONS

In a three-dose schedule (two primary doses and a booster), 40% doses of PCV13 were noninferior to full doses for all included serotypes. Lower doses of PCV13 and PCV10 did not meet the criteria for noninferiority.

DOI: NJ202409260000002

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2314620