The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review.

Olivia Falconer,Christine E Jones,Marie-Louise Newell

doi:10.3389/fimmu.2018.00328

Abstract

The success of prevention of mother to child transmission programs over the last two decades has led to an increasing number of infants who are exposed to human immunodeficiency virus (HIV), but who are not themselves infected (HIV-exposed, uninfected infants). Although the morbidity and mortality among HIV-exposed, uninfected infants is considerably lower than that among HIV-infected infants, they may remain at increased risk of infections in the first 2 years of life compared with their HIV-unexposed peers, especially in the absence of breastfeeding. There is some evidence of immunological differences in HIV-exposed, uninfected infants, which could play a role in susceptibility to infection. Cytomegalovirus (CMV) may contribute to the increased immune activation observed in HIV-exposed, uninfected infants. Infants born to HIV-infected women are at increased risk of congenital CMV infection, as well as early acquisition of postnatal CMV infection. In infants with HIV infection, CMV co-infection in early life is associated with higher morbidity and mortality. This review considers how HIV infection, HIV exposure, and CMV infection affect infant responses to vaccination, and explores possible immunological and other explanations for these findings. HIV-infected infants have lower vaccine-induced antibody concentrations following tetanus, diphtheria, pertussis, hepatitis B, and pneumococcal vaccination, although the clinical relevance of this difference is not known. Despite lower concentrations of maternal-specific antibody at birth, HIV-exposed, uninfected infants respond to vaccination at least as well as their HIV-unexposed uninfected peers. CMV infection leads to an increase in activation and differentiation of the whole T-cell population, but there is limited data on the effects of CMV infection on infant vaccine responses. In light of growing evidence of poor clinical outcomes associated with CMV infection in HIV-exposed, uninfected infants, further studies are particularly important in this group. A clearer understanding of the mechanisms by which maternal viral infections influence the developing infant immune system is critical to the success of maternal and infant vaccination strategies.

Highlights

Immunization is essential to global strategies to reduce infant mortality, especially in low-resource settings where infectious morbidity and mortality remain high (1, 2)
This review aimed to review the contemporary literature; there were no studies comparing vaccine responses of human immunodeficiency virus (HIV)-infected infants treated with antiretroviral therapy (ART) and HIV-exposed, uninfected infants, this comparison is not made in this review
As many of the infants in the studies reviewed were born to mothers who started ART a short time before delivery as part of prevention of mother-to-child transmission (PMTCT) programs, and were not exclusively breastfed, future studies will be needed to determine whether the same changes in immune responses are present when mothers and infants undertake optimal HIV treatment, PMTCT, and feeding practices

Summary

Introduction

Immunization is essential to global strategies to reduce infant mortality, especially in low-resource settings where infectious morbidity and mortality remain high (1, 2). In regions of the world where the burden of infectious diseases is high, even a small reduction in vaccine efficacy might have important clinical implications for young infants. Factors affecting infant vaccine responses can be divided into those relating to the infant, mother and environment; an important and potentially modifiable maternal factor is antenatal viral infections. Studies of the effects of maternal antenatal viral infections on infant vaccine responses have focused on two important viral infections: human immunodeficiency virus (HIV) and cytomegalovirus (CMV). In 2015, there were 1.4 million pregnant women living with HIV (3), and an estimated 24% of those did not receive antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) (4). In infants born with HIV infection, early commencement of combination ART significantly reduces mortality (5, 6) and is associated with increased magnitude and quality of infant antibody responses to vaccines (7–10), but there is some evidence of reduced humoral responses to vaccines even in those children starting ART at 6–8 weeks of age, compared with HIV-unexposed infants (9)

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