HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life.

Eunice W Nduati,Miguel G Knight,Irene N Nkumama,Amin S Hassan,Faith K Gambo,Margaret N Jahangir,Timothy J Etyang,Daniel M Muema,James A Berkley,Britta C Urban,H F Staats

doi:10.1128/cvi.00149-16

Abstract

Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected.

Highlights

The use of highly active antiretroviral therapy (HAART), improved obstetric management, and formula feeding have reduced vertical HIV infection to almost zero in the developed countries [1], with some progress being made in resource-poor countries [2]
While the available evidence has largely focused on the potential disruptions to the T-cell compartment in HIV-exposed uninfected (HEU) infants, much less is known about the impact of HIV exposure on the B-cell compartment, with a majority of the studies concentrating on serological parameters [10]
The study was conducted at the Comprehensive Care and Research Clinic (CCRC), Kilifi County Hospital (KCH), prior to the 2012 national integration of prevention of motherto-child transmission of HIV (PMTCT) services with mother-to-child health (MCH) services

Summary

Introduction

The use of highly active antiretroviral therapy (HAART), improved obstetric management, and formula feeding have reduced vertical HIV infection to almost zero in the developed countries [1], with some progress being made in resource-poor countries [2]. Of the few studies that have investigated the impact of HIV exposure on B cells, one reported increased B-cell apoptosis in HEU infants [27], whereas others observed a higher percentage of CD19ϩ cells [16, 28]. We sought to investigate the impact of maternal HIV infection on the infant’s developing B-cell compartment during the first 2 years of life by determining the phenotypic composition of the B-cell compartment and associating this with the induction and maintenance of antigen-specific memory B cells and antibodies in response to common childhood vaccines in HEU and HUU infants

Methods

Results

Conclusion