Negative Correlation between Circulating CD4+FOXP3+CD127− Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria–Tetanus–Pertussis Vaccine Implies a Regulatory Role

Abstract

Regulatory T cells (Tregs) play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP) and/or measles vaccine (MV). We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

Limited Impact of Human Cytomegalovirus Infection in African Infants on Vaccine-Specific Responses Following Diphtheria-Tetanus-Pertussis and Measles Vaccination

“…Gambians, the primary findings of which have been published previously (30,31). We investigated the effect of HCMV infection on responses to the two vaccines.…”

“…The infant characteristics at 9 months of age have been described elsewhere for this cohort of children (30,31). HCMV status was determined for 225 infants (108 females and 117 males) at 9 months of age for whom we had paired blood samples at 10 months of age, among whom 153 (68%) were found to be HCMV+ and 72 (32%) were HCMV-( Table 1).…”

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

“…There is a notable reduction in Treg cells post-surgery in patients undergoing tumor resection with general anesthesia [109][110][111]. Levels of Treg cells are implicated in vaccine immunogenicity [112], as well as the autoimmune sequelae of idiopathic thrombocytopenic purpura, which is correlated with vaccination or infection [113][114][115]. an increase in Th17/Treg ratio may lead to greater inflammation, resulting in enhanced pathogen clearance at the cost of greater susceptibility to bystander immunopathology [116][117][118].…”

Sex-Differential Impact of Human Cytomegalovirus Infection on In Vitro Reactivity to Toll-Like Receptor 2, 4 and 7/8 Stimulation in Gambian Infants

“…The 9-month old infants in this study were participating in a vaccine trial, the results of which have been published previously [ 28 , 30 ]. They were healthy afebrile male and female children recruited at the Sukuta Health Centre near the coast of The Gambia in West Africa.…”