B-cell development and pneumococcal immunity in vertically acquired HIV infection.

Area of Science:

• Immunology
• Virology
• Pediatrics

Background:

• Many children with human immunodeficiency virus (HIV) infection now survive into adulthood due to advancements in antiretroviral therapy (ART).
• The long-term impact of vertically acquired HIV on the development of humoral immunity in adults remains an area of active research.

Purpose of the Study:

• To explore the impact of vertically acquired HIV in the era of ART on humoral immunity development.
• To characterize and compare natural and vaccine-related immunity to pneumococcus and B-cell phenotype in young adults with vertically acquired HIV, horizontally acquired HIV, and healthy controls.

Main Methods:

• Serotype-specific pneumococcal (Pnc) immunoglobulin M and G concentrations were measured before and up to 1 year post-Pnc polysaccharide (Pneumovax) immunization.
• Opsonophagocytic activity, B-cell subpopulations, and dynamic markers of B-cell signaling, turnover, and apoptosis were evaluated using flow cytometry.

Main Results:

• HIV-infected patients exhibited impaired natural Pnc immunity and reduced humoral responses to Pneumovax immunization, most pronounced in viremic individuals.
• Early-life viral control (before age 10) diminished these immune deficits.
• Expanded populations of abnormally activated and immature B-cells were observed in both HIV-infected groups, with vertically infected patients showing particular vulnerability in marginal zone and switched memory B-cell populations.

Conclusions:

• Damage to B-cell memory populations and impaired natural and vaccine immunity to pneumococcus are evident in adults who acquired HIV vertically in childhood.
• Sustained viral control from early childhood may help to limit immune damage and optimize humoral immunity in adult life.