Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses

• Published in: Virologica Sinica Vol. 33; no. 6; pp. 502 - 514
• Main Authors: Yuan, Li, Chen, Wen-Jiang, Wang, Jia-Ye, Li, Yan, Tian, Dan, Wang, Ming-Xia, Yu, Hao-Tong, Xu, Ying-Chu, Li, Di, Zhuang, Min, Ling, Hong
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 14.12.2018; KeAi Publishing Communications Ltd
• Subjects: Antigens; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Germinal centers; Glycoprotein gp120; Hepatitis; Hepatitis B; Hepatitis B surface antigen; HIV; Human immunodeficiency virus; Immunization; Immunological memory; Lymph nodes; Lymphocytes; Lymphocytes B; Lymphocytes T; Major histocompatibility complex; Medical Microbiology; Memory cells; Microbial Genetics and Genomics; Microbiology; Oncology; PD-1 protein; Research Article; Virology; Human immunodeficiency virus type 1 envelope; Primary immune response; Programmed death-1 (PD-1); Hepatitis B surface antigen (HBsAg); Immune memory
• ISSN: 1674-0769; 1995-820X
• DOI: 10.1007/s12250-018-0074-6

The development of a vaccine based on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen (HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper (Tfh) cells, germinal centers, and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death (PD)-1 + T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center (GC) reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1 + T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.