A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates

免疫原性 病毒学 病毒释放 鼻腔给药 免疫 佐剂 病毒载量 接种疫苗 中和抗体 抗体 生物 免疫 疫苗效力 医学 免疫学 免疫系统 病毒
作者
Sarah N. Tedjakusuma,Colin A. Lester,Elena D. Neuhaus,Emery G. Dora,Samanta Gutierrez,Molly R. Braun,Sean N. Tucker,Becca A. Flitter
出处
期刊:Vaccines [Multidisciplinary Digital Publishing Institute]
卷期号:12 (2): 132-132
标识
DOI:10.3390/vaccines12020132
摘要

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge.
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