CanSino Biologics Research Center, Tianjin, PR China.
CanSino Biologics Research Center, Tianjin, PR China.
Vaccine. 2024 Feb 27;42(6):1292-1299. doi: 10.1016/j.vaccine.2024.01.073. Epub 2024 Jan 30.
BACKGROUND: The emergence and rapid spread of new mutant strains of SARS-CoV-2 necessitate the development of a new generation vaccine capable of neutralizing a broad range of variants. When the SARS-CoV-2 Omicron variant emerged, individuals in China had already received an inactivated (INA) or a type 5 adenovirus-vectored (Ad5) SARS-CoV-2 vaccine targeting the wild-type virus. We have recently developed a bivalent recombinant type 5 vaccine targeting both the wild-type strain and the Omicron variant (Ad5-nCoV/O). The objectives of this study were to assess the immunogenicity of the bivalent vaccine as a booster against both the wild type and the Omicron variant. METHODS: In the single immunization model, mice received one intramuscular immunization with monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. In the prime-boost model, mice were primed intramuscularly with an INA or Ad5-vectored vaccine targeting wild-type SARS-CoV-2, and then boosted intramuscularly or intranasally with heterologous or homologous INA or monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. The vaccine-induced antibody responses and cellular immune responses were measured using ELISA, pseudovirus-based neutralization assays, the intracellular cytokine staining (ICS) and ELISpot. RESULTS: Single-dose prime vaccination with the monovalent and bivalent vaccines elicited robust antibody responses and CD4 + and CD8 + cellular responses against the spike protein of WT and Omicron SARS-CoV-2. Both intramuscular and intranasal boost vaccination with the bivalent Ad5-nCoV/O following a prime with INA or Ad5-vectored vaccines induced strong serum neutralization antibody responses to both wild type and Omicron variants. A heterologous prime-boost vaccination elicited greater neutralization antibody responses than a homologous prime-boost vaccination when mice were boosted with Ad5-vectored vaccines following a prime with INA. Intranasal boost also resulted in significant mucosal IgA responses. CONCLUSION: The bivalent vaccine Ad5-nCoV/O exhibited robust immunogenicity, inducing broad-spectrum cross-neutralizing antibodies and cellular immune responses against both wild type and Omicron variants of SARS-CoV-2. The results demonstrated the potential of the bivalent vaccine in addressing the challenges posed by emerging SARS-CoV-2 Omicron variants.
背景：新的 SARS-CoV-2 突变株的出现和迅速传播，需要开发新一代能够中和广泛变异株的疫苗。当 SARS-CoV-2 的奥密克戎变异株出现时，中国的接种者已经接种了针对野生型病毒的灭活（INA）或 5 型腺病毒载体（Ad5）SARS-CoV-2 疫苗。我们最近开发了一种针对野生型和奥密克戎变异株的双价重组 5 型疫苗（Ad5-nCoV/O）。本研究的目的是评估该双价疫苗作为针对野生型和奥密克戎变异株的加强针的免疫原性。
方法：在单次免疫模型中，小鼠接受单剂量肌肉注射针对野生型 SARS-CoV-2 和奥密克戎变异株的单价或双价 Ad5 载体疫苗。在初免-加强免疫模型中，小鼠接受 INA 或 Ad5 载体疫苗针对野生型 SARS-CoV-2 的初免，然后肌肉注射或鼻腔内接种针对野生型 SARS-CoV-2 和奥密克戎变异株的异源或同源 INA 或单价或双价 Ad5 载体疫苗。使用 ELISA、假病毒中和试验、细胞内细胞因子染色（ICS）和 ELISpot 来测量疫苗诱导的抗体反应和细胞免疫反应。
结果：单剂量初免接种单价和双价疫苗可引起针对 WT 和奥密克戎 SARS-CoV-2 刺突蛋白的强烈抗体反应和 CD4+和 CD8+细胞反应。在 INA 或 Ad5 载体疫苗初免后，肌肉注射或鼻腔内接种双价 Ad5-nCoV/O 加强免疫，可诱导针对野生型和奥密克戎变异株的强烈血清中和抗体反应。当 INA 初免后，使用 Ad5 载体疫苗加强免疫时，异源初免-加强免疫产生的中和抗体反应大于同源初免-加强免疫。鼻腔内加强免疫也可引起显著的黏膜 IgA 反应。
结论：双价疫苗 Ad5-nCoV/O 表现出强大的免疫原性，可诱导针对 SARS-CoV-2 野生型和奥密克戎变异株的广谱交叉中和抗体和细胞免疫反应。结果表明，该双价疫苗在应对新出现的 SARS-CoV-2 奥密克戎变异株带来的挑战方面具有潜力。
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