本期文章：《新英格兰医学杂志》：Vol.389 No.3

美国辉瑞制药公司Annaliesa S. Anderson团队研究了母体接种婴儿B组链球菌疫苗的潜力。这一研究成果发表在2023年7月19日出版的《新英格兰医学杂志》上。

自然史研究表明，新生儿血清型特异性抗荚膜多糖（CPS）IgG与B组链球菌疾病风险降低相关。科学家正在开发一种六价CPS-交叉反应材料197复合糖疫苗（GBS6），作为预防幼儿侵袭性B组链球菌的母体疫苗。

在一项正在进行的涉及孕妇的2期安慰剂对照试验中，研究组评估了单剂量各种GBS6制剂的安全性和免疫原性，并分析了母体转移的抗CPS抗体。在同一人群中进行的一项平行血清流行病学研究中，他们评估了血清型特异性抗CPS IgG浓度，这些浓度与89天以下新生儿患侵袭性疾病的风险降低有关，以确定假定的保护阈值。

在血清流行病学研究中，自然获得的抗CPS IgG浓度与婴儿患病风险的降低有关。被确定与疾病风险降低75%至95%相关的IgG阈值为0.184至0.827微克/毫升。在母亲或婴儿中未观察到GBS6相关的安全信号。母亲和婴儿的不良事件和严重不良事件的发生率在试验组中相似；在接受含有磷酸铝的GBS6的组中观察到更多的局部反应。在婴儿中，最常见的严重不良事件是轻微的先天性畸形（脐疝和先天性真皮黑色素细胞增多症）。

GBS6诱导了对所有血清型的母体抗体反应，根据剂量的不同，母体与婴儿的抗体比率约为0.4至1.3。抗CPS IgG浓度高于0.184微克/毫升的婴儿的百分比因血清型和配方而异，57%至97%的婴儿对最具免疫原性的配方有血清反应。

研究结果表明，GBS6在孕妇中引发了针对B组链球菌的抗CPS抗体，这些抗体被水平转移到婴儿身上，可降低侵袭性B组链球菌疾病风险。

附：英文原文

Title: Potential for Maternally Administered Vaccine for Infant Group B Streptococcus

Author: Shabir A. Madhi, M.D., Ph.D.,, Annaliesa S. Anderson, Ph.D.,, Judith Absalon, M.D., M.P.H.,, David Radley, M.S.,, Raphael Simon, Ph.D.,, Babalwa Jongihlati, M.D.,, Renate Strehlau, M.D., Ph.D.,, Anika M. van Niekerk, M.D.,, Alane Izu, Ph.D.,, Niree Naidoo, M.D.,, Gaurav Kwatra, Ph.D.,, Yogandree Ramsamy, M.D., Ph.D.,, Mohamed Said, M.D.,, Stephanie Jones, M.D.,, Lisa Jose, M.D.,, Lee Fairlie, M.D.,, Shaun L. Barnabas, M.D., Ph.D.,, Ryan Newton, M.B.A.,, Samantha Munson, M.P.H.,, Zahra Jefferies, M.Sc.,, Danka Pavliakova, M.Sc.,, Natalie C. Silmon de Monerri, Ph.D.,, Emily Gomme, Ph.D.,, John L. Perez, M.D.,, Daniel A. Scott, M.D.,, William C. Gruber, M.D.,, and Kathrin U. Jansen, Ph.D.

Issue&Volume: 2023-07-19

Abstract:

BACKGROUND

Natural history studies have correlated serotype-specific anti–capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS–cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants.

METHODS

In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds.

RESULTS

Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 μg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 μg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation.

CONCLUSIONS

GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease.

DOI: 10.1056/NEJMoa2116045