Sui Yongjun, Li Jianping, Andersen Hanne, Zhang Roushu, Prabhu Sunaina K, Hoang Tanya, Venzon David, Cook Anthony, Brown Renita, Teow Elyse, Velasco Jason, Pessaint Laurent, Moore Ian N, Lagenaur Laurel, Talton Jim, Breed Matthew W, Kramer Josh, Bock Kevin W, Minai Mahnaz, Nagata Bianca M, Choo-Wosoba Hyoyoung, Lewis Mark G, Wang Lai-Xi, Berzofsky Jay A
Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
BIOQUAL Inc., Rockville, MD 20850, USA.
PNAS Nexus. 2022 Jun 17;1(3):pgac091. doi: 10.1093/pnasnexus/pgac091. eCollection 2022 Jul.
Emergence of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity pose threats to curbing the COVID-19 pandemic. Effective, safe, and convenient booster vaccines are in need. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is one of the hardest to cross-neutralize. Herein, we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. A total of 1 year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specific CD4 and CD8 T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated 1 year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现以及疫苗/感染诱导的免疫力减弱对控制新冠疫情构成了威胁。因此需要有效、安全且便捷的加强疫苗。我们推测，一种经过变体修饰的黏膜加强疫苗可能会诱导局部免疫，从而在病毒进入口预防SARS-CoV-2感染。β变体是最难被交叉中和的变体之一。在此，我们评估了由β变体刺突蛋白S1与白细胞介素-15（IL-15）和Toll样受体（TLR）激动剂组成的鼻内加强疫苗在先前免疫的猕猴中的保护效果。这些猕猴首先用含有相同佐剂的武汉株S1进行免疫接种。总共1年后，几乎检测不到SARS-CoV-2特异性抗体。然而，加强疫苗诱导了强烈的体液免疫，包括血清和支气管肺泡灌洗（BAL）中的IgG、鼻腔分泌物和BAL中的分泌型IgA，以及针对原始毒株和/或β变体的中和抗体。在外周血单核细胞（PBMC）和BAL中也引发了β变体S1特异性的CD4和CD8 T细胞反应。在接受SARS-CoV-2 β变体攻击后，接种疫苗的组在上呼吸道和下呼吸道均表现出对病毒复制的显著保护作用，在鼻腔中几乎具有完全保护作用。首次接种疫苗1年后进行一次鼻内β变体加强接种可引发针对β变体感染的保护性免疫这一事实，可能为未来SARS-CoV-2加强疫苗的设计和接种时间提供参考。
