A Beta Strain-Based Spike Glycoprotein Vaccine Candidate Induces Broad Neutralization and Protection against SARS-CoV-2 Variants of Concern

Cao, Lei; Guo, Jinyuan; Li, Hai; Ren, Hu; Xiao, Kang; Zhang, Yan; Zhu, Shuangli; Song, Yang; Zhao, Wei; Wu, Dan; Chen, Zhihui; Zhang, Yanan; Xia, Baicheng; Ji, Tianjiao; Yan, Dongmei; Wang, Dongyan; Yang, Qian; Zhou, Yangzi; Li, Xiaolei; Hou, Zhanjun; Xu, Wenbo

doi:10.1128/spectrum.02687-22

Cited by 2 publications

(1 citation statement)

References 51 publications

(41 reference statements)

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“…Newly developed SARS-CoV-2 vaccines can take consensus sites of majority variants ( 23 ) or use conserved S2 subunit of the spike protein ( 24 ). Alternatively, the potency of existing vaccines with the original strain antigens can be increased by adjuvant, resulting in a robust immune response that can effectively neutralize even variants that evade the immune system ( 23 , 25 – 28 ). Numerous studies have indicated that toll-like receptor (TLR) agonists are effective as mucosal adjuvants ( 29 – 31 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 spike-FLIPr fusion protein plus lipidated FLIPr protects against various SARS-CoV-2 variants in hamsters

Hsieh,

Hsu,

Liao

et al. 2024

J Virol

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Vaccine-induced mucosal immunity and broad protective capacity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remain inadequate. Formyl peptide receptor-like 1 inhibitory protein (FLIPr), produced by Staphylococcus aureus , can bind to various Fcγ receptor subclasses. Recombinant lipidated FLIPr (rLF) was previously found to be an effective adjuvant. In this study, we developed a vaccine candidate, the recombinant Delta SARS-CoV-2 spike (rDS)-FLIPr fusion protein (rDS-F), which employs the property of FLIPr binding to various Fcγ receptors. Our study shows that rDS-F plus rLF promotes rDS capture by dendritic cells. Intranasal vaccination of mice with rDS-F plus rLF increases persistent systemic and mucosal antibody responses and CD4/CD8 T-cell responses. Importantly, antibodies induced by rDS-F plus rLF vaccination neutralize Delta, Wuhan, Alpha, Beta, and Omicron strains. Additionally, rDS-F plus rLF provides protective effects against various SARS-CoV-2 variants in hamsters by reducing inflammation and viral loads in the lung. Therefore, rDS-F plus rLF is a potential vaccine candidate to induce broad protective responses against various SARS-CoV-2 variants. IMPORTANCE Mucosal immunity is vital for combating pathogens, especially in the context of respiratory diseases like COVID-19. Despite this, most approved vaccines are administered via injection, providing systemic but limited mucosal protection. Developing vaccines that stimulate both mucosal and systemic immunity to address future coronavirus mutations is a growing trend. However, eliciting strong mucosal immune responses without adjuvants remains a challenge. In our study, we have demonstrated that using a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-formyl peptide receptor-like 1 inhibitory protein (FLIPr) fusion protein as an antigen, in combination with recombinant lipidated FLIPr as an effective adjuvant, induced simultaneous systemic and mucosal immune responses through intranasal immunization in mice and hamster models. This approach offered protection against various SARS-CoV-2 strains, making it a promising vaccine candidate for broad protection. This finding is pivotal for future broad-spectrum vaccine development.

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