Why HIV Patients Have Reduced Flu Vaccine Response

As the name suggests, human immunodeficiency virus is all about lowered immunity.

As the name suggests, human immunodeficiency virus (HIV) is all about lowered immunity.

Its mechanism is B cell dysregulation, and drug treatment can restore most of the patient’s B cell function, but not all of it. Plus, the restoration’s permanence is unlikely, so eventually, the patient’s immune capacity will decline.

These changes can influence antibody responses to immunization profoundly. For example, influenza vaccines that successfully induce immunogenicity in those who don’t have HIV often induce a much lower response in HIV-infected individuals.

Recently, researchers determined why HIV-infected individuals have lower magnitude responses. In an article published in Nature: Scientific Reports, they explained that treatment doesn’t always restore vaccine responsiveness, and they described how HIV infection alters humoral immunity to seasonal influenza vaccines.

In their study, the researchers enrolled 26 HIV-positive patients receiving antiretroviral therapy and 30 healthy controls, all of whom had been vaccinated with the 2015 Southern Hemisphere trivalent inactivated influenza vaccine (IIV3). The study authors assessed serological and memory B cell responses.

A key reason for this specific investigation was that antigenic drift has forced vaccine reformulation that year, and the A/Switzerland/9715293/2013 strain was added to IIV3. A/Switzerland/9715293/2013 is an H3N2 virus, and the researchers hypothesized that this strain would be new to most participants.

HIV-positive and HIV-negative participants mounted similar serological responses to IIV3, but the researchers indicated that serological studies based on hemagglutination inhibition titers alone are insufficient to measure response.

Both cohorts also activated and expanded memory B cell populations specific for vaccine-component influenza strains. It was in this area that the researchers found a significant difference: HIV-positive patients developed lower peak frequencies of memory B cells than uninfected controls did.

Of note, all participants had some innate (baseline) immunity to the A/Switzerland/9715293/2013 strain. The researchers suggested that repeated lifetime exposures to historical H3N2 antigens seeds memory B cells with cross-reactivity to new H3N2 strains that undergo antigenic drift.

This research supports the need for annual IIV3 vaccination among HIV-infected individuals, as it re-establishes the B cell memory pool.

The research’s implications for vaccine developers include vaccine reformulation with components that can boost peak frequencies and repopulate influenza-specific B cell populations. For clinicians, these findings call for improved vaccination strategies.