Lenart Klara, Arcoverde Cerveira Rodrigo, Hellgren Fredrika, Ols Sebastian, Sheward Daniel J, Kim Changil, Cagigi Alberto, Gagne Matthew, Davis Brandon, Germosen Daritza, Roy Vicky, Alter Galit, Letscher Hélène, Van Wassenhove Jérôme, Gros Wesley, Gallouët Anne-Sophie, Le Grand Roger, Kleanthous Harry, Guebre-Xabier Mimi, Murrell Ben, Patel Nita, Glenn Gregory, Smith Gale, Loré Karin
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
Karolinska University Hospital, Stockholm, Sweden.
NPJ Vaccines. 2024 Jan 20;9(1):17. doi: 10.1038/s41541-024-00806-2.
The immune responses to Novavax's licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-M adjuvanted vaccines predominantly elicits immune events in local tissues with little spillover to the periphery. A third dose of an updated vaccine based on the Gamma (P.1) variant 7 months after two immunizations with licensed NVX-CoV2373 resulted in significant enhancement of anti-spike antibody titers and antibody breadth including neutralization of forward drift Omicron variants. The third immunization expanded the Spike-specific memory B cell pool, induced significant somatic hypermutation, and increased serum antibody avidity, indicating considerable affinity maturation. Seven months after immunization, vaccinated animals controlled infection by either WA-1 or P.1 strain, mediated by rapid anamnestic antibody and T cell responses in the lungs. In conclusion, a third immunization with an adjuvanted, low-dose recombinant protein vaccine significantly improved the quality of B cell responses, enhanced antibody breadth, and provided durable protection against SARS-CoV-2 challenge.
对诺瓦瓦克斯公司已获许可的NVX-CoV2373纳米颗粒刺突蛋白新冠疫苗的免疫反应仍未完全了解。在此，我们在恒河猴身上发现，用含Matrix-M佐剂的疫苗进行免疫主要在局部组织引发免疫反应，很少扩散到外周。在用已获许可的NVX-CoV2373进行两次免疫接种7个月后，接种一剂基于伽马（P.1）变体的更新疫苗，导致抗刺突抗体滴度和抗体广度显著增强，包括对正向漂移的奥密克戎变体的中和作用。第三次免疫接种扩大了刺突特异性记忆B细胞库，诱导了显著的体细胞超突变，并提高了血清抗体亲和力，表明有相当程度的亲和力成熟。免疫接种7个月后，接种疫苗的动物通过肺部快速的回忆性抗体和T细胞反应，控制了由WA-1或P.1毒株引起的感染。总之，用佐剂低剂量重组蛋白疫苗进行第三次免疫接种显著改善了B细胞反应的质量，增强了抗体广度，并提供了针对新冠病毒攻击的持久保护。
