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基于刺突蛋白和核衣壳的DNA疫苗联合免疫以获得针对SARS-CoV-2奥密克戎毒株的长期保护性免疫。

Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron.

作者信息

Pinto Paolla Beatriz Almeida, Timis Julia, Chuensirikulchai Kantinan, Li Qin Hui, Lu Hsueh Han, Maule Erin, Nguyen Michael, Alves Rúbens Prince Dos Santos, Verma Shailendra Kumar, Ana-Sosa-Batiz Fernanda, Valentine Kristen, Landeras-Bueno Sara, Kim Kenneth, Hastie Kathryn, Saphire Erica Ollmann, Alves Ada, Elong Ngono Annie, Shresta Sujan

机构信息

Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, 92037, USA.

Laboratory of Biotechnology and Physiology of Viral Infections, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, 21040-900, Brazil.

出版信息

NPJ Vaccines. 2024 Dec 19;9(1):252. doi: 10.1038/s41541-024-01043-3.

DOI:10.1038/s41541-024-01043-3
PMID:39702529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11659323/
Abstract

The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice. S, N, and S + N vaccines all elicited polyfunctional CD4 and CD8 T cell responses and provided short-term cross-protection against Beta and Omicron BA.2 variants, but only co-immunization with S + N vaccines provided long-term protection against Omicron BA.2. Depletion of CD4 and CD8 T cells reduced the long-term efficacy, demonstrating a crucial role for T cells in the durability of protection. These findings underscore the potential to enhance long-lived protection against SARS-CoV-2 variants by combining S and N antigens in next-generation COVID-19 vaccines.

摘要

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的持续演变对现有的基于刺突蛋白（S）的新冠疫苗的持久性构成挑战。我们推测，与基于S的疫苗相比，由S和核衣壳（N）抗原组成的疫苗将通过增强和扩大细胞免疫来提高保护的持久性。为了验证这一点，我们研究了野生型SARS-CoV-2基于S和N的DNA疫苗单独或联合接种给K18-hACE2小鼠后的免疫原性和效力。S、N和S+N疫苗均引发了多功能CD4和CD8 T细胞反应，并提供了针对贝塔和奥密克戎BA.2变体的短期交叉保护，但只有S+N疫苗联合免疫提供了针对奥密克戎BA.2的长期保护。CD4和CD8 T细胞的耗竭降低了长期效力，证明T细胞在保护的持久性中起关键作用。这些发现强调了在下一代新冠疫苗中通过结合S和N抗原增强对SARS-CoV-2变体的长期保护的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/2773078a2eb1/41541_2024_1043_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/4c66ff8cdab8/41541_2024_1043_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/22522c4526d4/41541_2024_1043_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/e13e647de770/41541_2024_1043_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/7b898c1b8d6e/41541_2024_1043_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/55b45860bec4/41541_2024_1043_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/2773078a2eb1/41541_2024_1043_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/4c66ff8cdab8/41541_2024_1043_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/22522c4526d4/41541_2024_1043_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/e13e647de770/41541_2024_1043_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/7b898c1b8d6e/41541_2024_1043_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/55b45860bec4/41541_2024_1043_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7be1/11659323/2773078a2eb1/41541_2024_1043_Fig6_HTML.jpg

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