Increased Influenza-Specific Antibody Avidity in HIV-Infected Women Compared With HIV-infected Men on Antiretroviral Therapy

Zhenwu Luo; Elizabeth Ogunrinde; Min Li; Lumin Zhang; Lisa Martin; Zejun Zhou; Zhiliang Hu; Tao Zhang; Zhen Li; Jiafeng Zhang; Bin Su; Tong Zhang; Hao Wu; Lei Ma; Guoyang Liao; Allison Ross Eckard; Maria Anna Julia Westerink; Sonya L. Heath; Wei Jiang

Disclosures

AIDS. 2019;33(1):33-44. 

In This Article

Abstract and Introduction

Abstract

Background: It is recommended that HIV-infected individuals receive annual influenza vaccination due to their high susceptibility to influenza infection, especially among women. However, there have been few studies investigating sex-related responses to influenza vaccine in antiretroviral therapy (ART)-treated HIV-infected individuals.

Method: In this study, 26 aviremic ART-treated HIV-infected individuals and 16 healthy controls were enrolled in the current study. Blood was collected prior to vaccination (D0), on days 7–10 (D7) and on days 14–21 (D14) following administration of the 2013–2014 seasonal influenza vaccine. A series of analyses evaluated the serological and cellular responses following influenza vaccination.

Results: Female HIV-infected individuals had increased influenza-specific antibody avidity relative to male HIV-infected individuals, but similar plasma levels of influenza-specific binding antibodies and neutralizing antibodies. Increased cycling B cells and follicular helper CD4+ T (Tfh) cells were observed in female HIV-infected individuals pre and postvaccination compared with male HIV-infected individuals, and cycling Tfh cells were directly correlated with influenza-specific antibody avidity. Moreover, plasma testosterone levels were inversely correlated with antibody avidity index. The magnitude of microbial translocation [plasma lipopolysaccharide (LPS)] level was directly correlated with influenza-specific antibody avidity. Circulating 16S rDNA microbiome showed that enrichment of specific species within Proteobacteria was associated with influenza-specific antibody avidity. These results, including differences based on sex and correlations, were only observed in HIV-infected individuals but not in the healthy controls.

Conclusion: This study demonstrated sex differences in influenza-specific antibody avidity in ART-treated HIV disease, and provides valuable information on vaccination strategy in the ART-treated HIV-infected population.

Introduction

HIV-1 infection is associated with an elevated incidence of influenza infection especially in women.[1] Seasonal influenza vaccination is highly recommended for all HIV-infected individuals[2] due to its ability to prevent influenza infection and reduce influenza-related morbidity and mortality.[3] It is unclear, however, whether there is a difference in the immune response to the influenza vaccine between men and women in this patient population.

Sex differences in immune responses against infectious diseases and vaccines have been shown among various populations in previous studies.[4] In general, men are more susceptible and experience more severe infections caused by parasites, fungi, bacteria and viruses due to their weak immune responses to these pathogens than women.[5] Moreover, many studies in healthy populations have found that women develop more robust antibody responses to vaccination than men.[6–8] However, women also develop higher inflammatory responses to vaccination, which result in increased adverse biological reactions to vaccination compared with men.[9]

During the 2009 H1N1 pandemic, women showed a higher mortality rate after exposure to the pathogenic influenza A virus than men.[10] This paradoxical effect may be related to the development of immune-mediated diseases during influenza infection that occur more frequently in women.[11] The increased risk of autoimmune diseases in women further supports this hypothesis.[12]

The purpose of the current study was to evaluate the difference in antibody response for men versus women in both HIV-infected individuals and healthy controls and characterize and link T and B cellular responses to serologic antibody responses. Understanding the immune perturbations in HIV can help improve the immunogenicity of vaccine regimens and establish guidelines to improve immune responses in this vulnerable population.

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