Analysis of protective immune responses to seasonal influenza vaccination in HIV-infected individuals

ABSTRACT

Owing to their increased susceptibility to influenza infection, HIV+ individuals are recommended to receive annual influenza vaccination. However, influenza vaccination induced production of anti-influenza neutralization antibodies (Nab) is successful only in some viral-suppressed antiretroviral therapy (ART) treated HIV+ subjects. Additionally, the mechanism of antibody response induced by influenza vaccine in antiretroviral-treated HIV+ subjects is unclear. In this study, we conducted a cohort study which contains 40 HIV+ ART-treated individuals to whom one dose of seasonal influenza vaccine was administered. Blood samples were collected on day 0, 7, 14, and 28 post-vaccination, and serologic responses were characterized by ELISA and micro-neutralization to measure the total antibodies and Nab against influenza vaccines. Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) and immunological assays was measured. Increased levels of proliferation of CD4+T cells and B cells with their corresponding subtypes were observed in HIV-infected subjects at day 7 (D7) following vaccination compared to pre-vaccination. Moreover, proliferation of CD4+T cells and B cells (D7) was correlated with influenza-specific H1N1 Nab at day 28 (D28). Our study could also demonstrate that apoptosis of CD4+T cells and B cells (D7) were inversely correlated with influenza-specific H1N1 Nab. Based on the Nab response after vaccination to each influenza subtypes (D28), HIV+ subjects were stratified as influenza vaccine responders and influenza vaccine non-responders (“responders” ≥ 4-fold increase from day 0; “non-responders” < 4-fold increase from day 0). A selected list of biological pathways (H1N1and H3N2: olfactory transduction, B: phagosome) enriched with transcripts were significantly altered in (ART) treated HIV+ subjects among Nab production responders. This study demonstrated a more detailed mechanism of immune regulation on influenza induced antibody response and revealed some knowledge regarding bioinformatics of vaccine responders and non-responder in influenza induced antibody production in ART-treated HIV patients.

KEYWORDS:

• ART-treated HIV patients
• neutralization antibody
• vaccination

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Authorship

Shenghui Qin conceived of and directed the project, wrote the manuscript. Xia Ying and Fuli Mi performed the laboratory sample testing and analyses. Xia Ying and Guoqiang Du were involved in critically revising the manuscript.

Accession numbers

Microarray data are available in GEO (Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=348922) with the accession number E-MTAB-8084.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.