The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals

Vaccine. 2017 Feb 1;35(5):831-841. doi: 10.1016/j.vaccine.2016.12.026. Epub 2016 Dec 22.

Abstract

Background: Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART).

Methods: 16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7-10 (D7) and 14-21 (D14) following the 2013-2014 seasonal influenza vaccine administrations. Subjects were classified as responders if neutralizing titers against H1N1 virus increased ⩾4-fold at D14 compared to D0. A serial analysis of B and CD4+ T cell frequencies and activation was performed on D0 and D7 by flow cytometry.

Results: 9 of 26 (34.6%) HIV-infected individuals and 7 of 16 (43.8%) healthy controls were classified as responders to influenza vaccines. Total B cell apoptosis (annexin V) was increased on D7 post-vaccination in non-responders but not in responders among both controls and HIV+ subjects. Surface CD80 expression on memory B cells and intracellular CD40L expression on memory CD4+ T cells were induced on D7 in responders of controls but not in non-responders. The CD80 and CD40L induction was not demonstrable in HIV-infected subjects regardless of responders and non-responders. Memory CD4+ T cell cycling tended to increase on D7 in the four study groups but did not achieve significance. All the other parameters were indistinguishable between responders and non-responders, regardless of HIV-infection status.

Conclusion: The perturbation of activation and apoptotic induction on B cells or CD4+ T cells after seasonal influenza vaccination in non-responders and HIV-infected subjects may help understand the mechanism of impaired vaccine responsiveness.

Keywords: B cells; HIV disease; Immunologic responders and non-responders; Influenza vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Viral / biosynthesis*
  • Antiretroviral Therapy, Highly Active
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology
  • Case-Control Studies
  • Female
  • Gene Expression
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / immunology
  • Humans
  • Immunologic Memory
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Male
  • Middle Aged
  • Seasons
  • Vaccination*

Substances

  • Anti-HIV Agents
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • B7-1 Antigen
  • Influenza Vaccines
  • CD40 Ligand