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

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.

Elimination of Vertical Transmission of Hepatitis B in Africa: A Review of Available Tools and New Opportunities

“…Infants with HIV-infection appear to develop lower antibody levels in response to HBV vaccine but vaccination recommendations are unchanged. 61 Studies show that the duration of the protective response after completion of the primary HBV vaccine series is long lasting (>20-30 years), in areas of both high and low endemnicity. 13,14,62–65 A booster dose of HBV is not recommended, but since 5% of infants do not respond to vaccine, a search for underlying immunologic or genetic differences in this group is ongoing.…”

Cytomegalovirus-Mediated T Cell Receptor Repertoire Perturbation Is Present in Early Life

“…In contrast to old age, the architecture, stability and composition of the TCR repertoire in infancy remains poorly understood due to the scarcity of deep sequencing studies conducted with paediatric samples ( 28 , 29 ). Several small-scale studies have looked at the composition of the foetal repertoire ( 30 ), although very few were carried out at the deep sequencing level ( 20 ).…”

How the gut microbiome regulates host immune responses to viral vaccines

“…In agreement with these observations, celiac disease patients have decreased seroconversion to hepatitis B vaccine [24 • ]. Also, chronic infections with many viruses including human cytomegalovirus and human immunodeficiency virus induce immune suppression decreasing the effectiveness of many vaccines [25]. However studies on the interactions between the resident virome and host immune function are scarce [26,27].…”