Carboni Filippo, Cozzi Roberta, Romagnoli Giacomo, Tuscano Giovanna, Balocchi Cristiana, Buffi Giada, Bodini Margherita, Brettoni Cecilia, Giusti Fabiola, Marchi Sara, Brogioni Giulia, Brogioni Barbara, Cinelli Paolo, Cappelli Luigia, Nocciolini Chiara, Senesi Silvia, Facciotti Claudia, Frigimelica Elisabetta, Fabbrini Monica, Stranges Daniela, Savino Silvana, Maione Domenico, Adamo Roberto, Wizel Benjamin, Margarit Immaculada, Romano Maria Rosaria
GSK, Siena, Italy.
GSK, Rockville, MD, USA.
NPJ Vaccines. 2023 Oct 6;8(1):152. doi: 10.1038/s41541-023-00744-5.
A maternal vaccine to protect neonates against Group B Streptococcus invasive infection is an unmet medical need. Such a vaccine should ideally be offered during the third trimester of pregnancy and induce strong immune responses after a single dose to maximize the time for placental transfer of protective antibodies. A key target antigen is the capsular polysaccharide, an anti-phagocytic virulence factor that elicits protective antibodies when conjugated to carrier proteins. The most prevalent polysaccharide serotypes conjugated to tetanus or diphtheria toxoids have been tested in humans as monovalent and multivalent formulations, showing excellent safety profiles and immunogenicity. However, responses were suboptimal in unprimed individuals after a single shot, the ideal schedule for vaccination during the third trimester of pregnancy. In the present study, we obtained and optimized self-assembling virus-like particles conjugated to Group B Streptococcus capsular polysaccharides. The resulting glyco-nanoparticles elicited strong immune responses in mice already after one immunization, providing pre-clinical proof of concept for a single-dose vaccine.
一种保护新生儿免受B族链球菌侵袭性感染的母体疫苗是尚未满足的医学需求。理想情况下，这种疫苗应在妊娠晚期接种，并在单剂量后诱导强烈的免疫反应，以最大限度地延长保护性抗体通过胎盘转移的时间。一个关键的靶抗原是荚膜多糖，这是一种抗吞噬毒力因子，与载体蛋白结合时可引发保护性抗体。与破伤风或白喉类毒素结合的最常见多糖血清型已作为单价和多价制剂在人体中进行了测试，显示出极佳的安全性和免疫原性。然而，对于未接种过疫苗的个体，在单次注射后反应并不理想，而这是妊娠晚期理想的疫苗接种方案。在本研究中，我们获得并优化了与B族链球菌荚膜多糖结合的自组装病毒样颗粒。由此产生的糖纳米颗粒在小鼠单次免疫后就引发了强烈的免疫反应，为单剂量疫苗提供了临床前概念验证。
