1. Academic Validation
  2. CRM197-conjugated multi antigen dominant epitope for effective human cytomegalovirus vaccine development

CRM197-conjugated multi antigen dominant epitope for effective human cytomegalovirus vaccine development

  • Int J Biol Macromol. 2022 Oct 14;S0141-8130(22)02351-0. doi: 10.1016/j.ijbiomac.2022.10.105.
Shasha Jiang 1 Fulong Nan 1 Shuyun Zhang 1 Xianjuan Zhang 1 Zonghui Li 1 Zhongjie Yu 1 Fengjun Liu 1 Jun Li 1 Xiaoqiong Zhou 1 Delei Niu 1 Hui Wang 1 Xueming Zhang 1 Wenxuan Liu 1 Xiaoli Yang 1 Bin Wang 2
Affiliations

Affiliations

  • 1 Department of Pathogenic Biology, Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao 266000, China.
  • 2 Department of Pathogenic Biology, Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao 266000, China. Electronic address: [email protected].
Abstract

Human cytomegalovirus (HCMV) Infection is a major cause of neonatal neurodevelopmental disorders and serious complications in organ transplantation. Previous HCMV vaccines focused on humoral immunity but had limited effect on viral Infection. T-cell responses are essential to prevent HCMV Infection, indicating that effective vaccines require T cells activation. In this study, we designed a novel polypeptides vaccine conjugated to a CRM197 carrier protein, encoding 15 CD8+ T-cell epitopes, five CD4+ T-cell epitopes, and four B-cell epitopes from gB287-320 and pp150311-325 of HCMV to induce T-cell immune responses. To evaluate the effectiveness of vaccines, we subsequently measured the expression of surface molecule markers and proinflammatory cytokines from antigen presenting cells in vivo and in vitro as well as the activation of T cells and Antibodies. The results demonstrated that this polypeptide vaccine could activate innate immunity including up-regulating MHCI, II, CD80, CD86, and cytokine expression through the TLR4/NF-κB pathway. Meanwhile, vaccinations elicited potent neutralizing antibody and cellular immune responses producing TNF-α, INF-γ and IL-2, indicating Th1-biased polarization. This finding underlines that CRM197-conjugated polypeptide vaccines facilitate a synergism of humoral and cellular immunity, providing enhanced protection against HCMV, which could be a potential strategy to prevent CMV-associated diseases.

Keywords

Cytomegalovirus; Peptide vaccine; T cells response.

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