Lovastatin enhances humoral and cellular immune responses to H1N1 influenza vaccine

被引:1
作者
Song, Zuchen [1 ,3 ]
Zhou, Yantong [1 ,3 ]
Jiao, Lina [1 ,3 ]
Zhu, Tianyu [1 ,3 ]
Yu, Ruihong [1 ,3 ]
Wang, Zheng [1 ,3 ]
Qiu, Yawei [3 ]
Miao, Jinfeng [3 ]
Cai, Ting [2 ]
Zhang, Shun [2 ]
Liu, Huina [2 ]
Sun, Haifeng [4 ]
Sun, Yuechao [2 ]
Wang, Deyun [1 ,3 ]
Liu, Zhenguang [1 ,2 ,3 ]
机构
[1] Nanjing Agr Univ, Inst Tradit Chinese Vet Med, Coll Vet Med, Nanjing 210095, Peoples R China
[2] Guoke Ningbo Life Sci & Hlth Ind Res Inst, Ningbo 315032, Zhejiang, Peoples R China
[3] Nanjing Agr Univ, Coll Vet Med, Joint Int Res Lab Anim Hlth & Food Safety, MOE, Nanjing 210095, Peoples R China
[4] Nanjing Agr Univ, Coll Vet Med, Minist Agr, Key Lab Bacteriol, Nanjing 210095, Peoples R China
关键词
Lovastatin; Vaccine; Immune responses; ADJUVANTS ALUMINUM; T-CELLS; MECHANISMS; HYDROXIDE;
D O I
10.1016/j.vetmic.2024.110331
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 (IFN gamma, TNF alpha) 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.
引用
收藏
页数:12
相关论文
共 40 条
[1]   Novel cellular and molecular mechanisms of induction of immune responses by aluminum adjuvants [J].
Aimanianda, Vishukumar ;
Haensler, Jean ;
Lacroix-Desmazes, Sebastien ;
Kaveri, Srini V. ;
Bayry, Jagadeesh .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2009, 30 (06) :287-295
[2]   Alum boosts TH2-type antibody responses to whole-inactivated virus influenza vaccine in mice but does not confer superior protection [J].
Bungener, Laura ;
Geeraedts, Felix ;
Ter Veer, Wouter ;
Medema, Jeroen ;
Wilschut, Jan ;
Huckriede, Anke .
VACCINE, 2008, 26 (19) :2350-2359
[3]   Cryomicroscopy provides structural snapshots of influenza virus membrane fusion [J].
Calder, Lesley J. ;
Rosenthal, Peter B. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2016, 23 (09) :853-858
[4]   Factors That Govern the Induction of Long-Lived Antibody Responses [J].
Chackerian, Bryce ;
Peabody, David S. .
VIRUSES-BASEL, 2020, 12 (01)
[5]   Adjuvants for swine vaccines: Mechanisms of actions and adjuvant effects [J].
Charerntantanakul, Wasin .
VACCINE, 2020, 38 (43) :6659-6681
[6]   A brief history of T cell help to B cells [J].
Crotty, Shane .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (03) :185-189
[7]   B Cell Responses: Cell Interaction Dynamics and Decisions [J].
Cyster, Jason G. ;
Allen, Christopher D. C. .
CELL, 2019, 177 (03) :524-540
[8]   Memories that last: Dynamics of memory T cells throughout the body [J].
Derksen, Lyanne Y. ;
Tesselaar, Kiki ;
Borghans, Jose A. M. .
IMMUNOLOGICAL REVIEWS, 2023, 316 (01) :38-51
[9]   In vitro and ex vivo analyses of co-infections with swine influenza and porcine reproductive and respiratory syndrome viruses [J].
Dobrescu, I. ;
Levast, B. ;
Lai, K. ;
Delgado-Ortega, M. ;
Walker, S. ;
Banman, S. ;
Townsend, H. ;
Simon, G. ;
Zhou, Y. ;
Gerdts, V. ;
Meurens, F. .
VETERINARY MICROBIOLOGY, 2014, 169 (1-2) :18-32
[10]   Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics [J].
Friess, Mona C. ;
Kritikos, Ioannis ;
Schineis, Philipp ;
Medina-Sanchez, Jessica Danielly ;
Gkountidi, Anastasia-Olga ;
Vallone, Angela ;
Sigmund, Elena C. ;
Schwitter, Corina ;
Vranova, Martina ;
Matti, Christoph ;
Arasa, Jorge ;
Demir, Cansaran Saygili ;
Bovay, Esther ;
Proulx, Steven T. ;
Tomura, Michio ;
Rot, Antal ;
Legler, Daniel F. ;
Petrova, Tatiana, V ;
Halin, Cornelia .
CELL REPORTS, 2022, 38 (05)