Song Zuchen, Zhou Yantong, Jiao Lina, Zhu Tianyu, Yu Ruihong, Wang Zheng, Qiu Yawei, Miao Jinfeng, Cai Ting, Zhang Shun, Liu Huina, Sun Haifeng, Sun Yuechao, Wang Deyun, Liu Zhenguang
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
Vet Microbiol. 2025 Jan;300:110331. doi: 10.1016/j.vetmic.2024.110331. Epub 2024 Dec 9.
The Swine Influenza Virus (SIV) is a major respiratory pathogen in swine, causing acute, febrile, and highly transmissible infections. This virus is widespread globally and poses significant risks to human health and social development. Traditional prevention strategies for SIV rely on the use of inactivated vaccines combined with Alum adjuvants. However, this method is limited by insufficient protection due to the lack of cellular immunity provided by Alum adjuvants. In this study, we investigated the effect of lovastatin, a specific inhibitor of the mevalonate pathway, on the immune response in mice vaccinated with the H1N1 vaccine. We focused on its impact on antibody production, as well as T-cell and B-cell development. Our findings reveal that the combination of lovastatin and H1N1 vaccine (Lov/H1N1) significantly enhances the production of H1N1-specific serum IgG and hemagglutination inhibition (HI) antibodies. Additionally, it promotes T-cell activation in both draining lymph nodes (dLNs) and the spleen. Analysis of cytokines produced after antigenic restimulation of splenic lymphocytes from immunized mice showed that the Lov/H1N1 combination induces both Th1-type (IFNγ, TNFα) and Th2-type (IL4, IL6) responses. Moreover, Lov/H1N1 facilitates the formation of germinal centers (GCs), which are crucial for the generation of memory B cells and long-lived plasma cells. These results indicate that lovastatin is a promising adjuvant candidate, capable of inducing robust cellular and humoral immune responses, thereby overcoming the limitations of Alum adjuvants. Our study provides a foundation for future research on combined vaccine strategies, highlighting Lovastatin's potential to enhance vaccine efficacy through improved immune responses.
猪流感病毒（SIV）是猪的主要呼吸道病原体，可引起急性、发热性且传播性很强的感染。这种病毒在全球广泛传播，对人类健康和社会发展构成重大风险。传统的SIV预防策略依赖于使用与铝佐剂联合的灭活疫苗。然而，由于铝佐剂缺乏细胞免疫，这种方法的保护作用有限。在本研究中，我们调查了甲羟戊酸途径的特异性抑制剂洛伐他汀对接种H1N1疫苗的小鼠免疫反应的影响。我们重点关注其对抗体产生以及T细胞和B细胞发育的影响。我们的研究结果表明，洛伐他汀与H1N1疫苗联合使用（Lov/H1N1）可显著提高H1N1特异性血清IgG和血凝抑制（HI）抗体的产生。此外，它还能促进引流淋巴结（dLNs）和脾脏中的T细胞活化。对免疫小鼠脾脏淋巴细胞进行抗原再刺激后产生的细胞因子分析表明，Lov/H1N1组合可诱导Th1型（IFNγ、TNFα）和Th2型（IL4、IL6）反应。此外，Lov/H1N1有助于生发中心（GCs）的形成，而生发中心对于记忆B细胞和长寿浆细胞的产生至关重要。这些结果表明，洛伐他汀是一种很有前景的佐剂候选物，能够诱导强大的细胞免疫和体液免疫反应，从而克服铝佐剂的局限性。我们的研究为未来联合疫苗策略的研究奠定了基础，突出了洛伐他汀通过改善免疫反应提高疫苗效力的潜力。
