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衰老恒河猴针对 BBV152(一种灭活的 SARS-CoV-2 疫苗)的宿主免疫反应,以及与β和δ变异株的交叉中和作用。

Host immune responses in aged rhesus macaques against BBV152, an inactivated SARS-CoV-2 vaccine, and cross-neutralization with beta and delta variants.

机构信息

Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, India.

出版信息

Front Immunol. 2023 Apr 28;14:1161571. doi: 10.3389/fimmu.2023.1161571. eCollection 2023.


DOI:10.3389/fimmu.2023.1161571
PMID:37187744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10175569/
Abstract

The magnitude and duration of immune response to COVID-19 vaccination in older adults are known to be adversely affected due to immunosenescence and inflammaging. The threat of emerging variants warrants studies on immune response in older adults to primary vaccination and booster doses so as to understand the effectiveness of vaccines in countering the threat of emerging variants. Non-human primates (NHPs) are ideal translational models, as the immunological responses in NHPs are similar to those in humans, so it enables us to understand host immune responses to the vaccine. We initially studied humoral immune responses in aged rhesus macaques employing a three-dose regimen of BBV152, an inactivated SARS-CoV-2 vaccine. Initially, the study investigated whether the third dose enhances the neutralizing antibody (Nab) titer against the homologous virus strain (B.1) and variants of concern (Beta and Delta variants) in aged rhesus macaques immunized with BBV152, adjuvanted with Algel/Algel-IMDG (imidazoquinoline). Later, we also attempted to understand cellular immunity in terms of lymphoproliferation against γ-inactivated SARS-CoV-2 B.1 and delta in naïve and vaccinated rhesus macaques after a year of the third dose. Following the three-dose regimen with 6 µg of BBV152 with Algel-IMDG, animals had increased Nab responses across all SARS-CoV-2 variants studied, which suggested the importance of booster dose for the enhanced immune response against SARS-CoV-2-circulating variants. The study also revealed the pronounced cellular immunity against B.1 and delta variants of SARS-CoV-2 in the aged rhesus macaques even after a year of vaccination.

摘要

众所周知,由于免疫衰老和炎症衰老,老年人对 COVID-19 疫苗的免疫反应的幅度和持续时间受到不利影响。新出现的变异体的威胁需要研究老年人对初级疫苗接种和加强剂量的免疫反应,以便了解疫苗对抗新出现的变异体威胁的有效性。非人类灵长类动物(NHP)是理想的转化模型,因为 NHP 的免疫反应与人类相似,因此我们能够了解宿主对疫苗的免疫反应。我们最初使用 BBV152(一种灭活的 SARS-CoV-2 疫苗)对老年恒河猴进行了三剂方案研究,以研究体液免疫反应。最初,该研究调查了在 BBV152 免疫的老年恒河猴中,第三剂是否增强了针对同源病毒株(B.1)和关注变异株(Beta 和 Delta 变异株)的中和抗体(Nab)滴度,佐剂为 Algel/Algel-IMDG(咪唑并喹啉)。后来,我们还试图了解一年后第三剂后针对 γ-灭活的 SARS-CoV-2 B.1 和 delta 的淋巴增殖的细胞免疫。在 Algel-IMDG 存在的情况下,用 6 µg 的 BBV152 进行三剂方案后,所有研究的 SARS-CoV-2 变异体中,动物的 Nab 反应均增加,这表明加强剂量对增强针对 SARS-CoV-2 循环变异体的免疫反应很重要。该研究还揭示了即使在接种疫苗一年后,老年恒河猴对 SARS-CoV-2 的 B.1 和 delta 变异体仍具有明显的细胞免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/9c277bea31be/fimmu-14-1161571-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/9f43a61bf502/fimmu-14-1161571-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/0794b39c21c0/fimmu-14-1161571-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/9c277bea31be/fimmu-14-1161571-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/9f43a61bf502/fimmu-14-1161571-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/0794b39c21c0/fimmu-14-1161571-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cff/10175569/9c277bea31be/fimmu-14-1161571-g003.jpg

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引用本文的文献

[1]
Harnessing cellular immunity for next-generation vaccines against respiratory viruses: mechanisms, platforms, and optimization strategies.

Front Immunol. 2025-8-13

本文引用的文献

[1]
Evaluation of immunogenicity post two doses of inactivated SARS-CoV-2 vaccine, Covaxin after six months.

Hum Vaccin Immunother. 2022-12-30

[2]
Protective efficacy of COVAXIN® against Delta and Omicron variants in hamster model.

iScience. 2022-10-21

[3]
Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques.

Signal Transduct Target Ther. 2022-4-18

[4]
Booster dose of the inactivated COVID-19 vaccine BBV152 (Covaxin) enhances the neutralizing antibody response against Alpha, Beta, Delta and Omicron variants of concern.

J Travel Med. 2022-5-31

[5]
Elevated neutralization of Omicron with sera of COVID-19 recovered and breakthrough cases vaccinated with Covaxin than two dose naïve vaccinees.

J Infect. 2022-6

[6]
Three doses of prototypic SARS-CoV-2 inactivated vaccine induce cross-protection against its variants of concern.

Signal Transduct Target Ther. 2022-2-25

[7]
Population antibody responses following COVID-19 vaccination in 212,102 individuals.

Nat Commun. 2022-2-16

[8]
Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine-boosted nonhuman primates.

Science. 2021-12-10

[9]
Antibody response after first and second-dose of ChAdOx1-nCOV (Covishield®) and BBV-152 (Covaxin®) among health care workers in India: The final results of cross-sectional coronavirus vaccine-induced antibody titre (COVAT) study.

Vaccine. 2021-10-22

[10]
Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine BBV152/Covaxin.

J Travel Med. 2021-10-11

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