Characterization of the Infant Immune System and the Influence and Immunogenicity of BCG Vaccination in Infant and Adult Rhesus Macaques

Charlotte Sarfas*, Andrew D. White, Laura Sibley, Alexandra L. Morrison, Jennie Gullick, Steve Lawrence, Mike J. Dennis, Philip D. Marsh, Helen A. Fletcher, Sally A. Sharpe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In many countries where tuberculosis (TB) is endemic, the Bacillus Calmette–Guérin (BCG) vaccine is given as close to birth as possible to protect infants and children from severe forms of TB. However, BCG has variable efficacy and is not as effective against adult pulmonary TB. At present, most animal models used to study novel TB vaccine candidates rely on the use of adult animals. Human studies show that the infant immune system is different to that of an adult. Understanding how the phenotypic profile and functional ability of the immature host immune system compares to that of a mature adult, together with the subsequent BCG immune response, is critical to ensuring that new TB vaccines are tested in the most appropriate models. BCG-specific immune responses were detected in macaques vaccinated within a week of birth from six weeks after immunization indicating that neonatal macaques are able to generate a functional cellular response to the vaccine. However, the responses measured were significantly lower than those typically observed following BCG vaccination in adult rhesus macaques and infant profiles were skewed towards the activation and attraction of macrophages and monocytes and the synthesis in addition to release of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α. The frequency of specific immune cell populations changed significantly through the first three years of life as the infants developed into young adult macaques. Notably, the CD4:CD8 ratio significantly declined as the macaques aged due to a significant decrease in the proportion of CD4+ T-cells relative to a significant increase in CD8+ T-cells. Also, the frequency of both CD4+ and CD8+ T-cells expressing the memory marker CD95, and memory subset populations including effector memory, central memory and stem cell memory, increased significantly as animals matured. Infant macaques, vaccinated with BCG within a week of birth, possessed a significantly higher frequency of CD14+ classical monocytes and granulocytes which remained different throughout the first three years of life compared to unvaccinated age matched animals. These findings, along with the increase in monokines following vaccination in infants, may provide an insight into the mechanism by which vaccination with BCG is able to provide non-specific immunity against non-mycobacterial organisms.

Original languageEnglish
Article number754589
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 11 Oct 2021

Bibliographical note

Funding Information: This work was support by funding awarded from Aeras Global Tb Foundation, EU Commission H2020 project 730964 TRANSVAC2, UK Department of Health.

Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Publisher Copyright: © Copyright © 2021 Sarfas, White, Sibley, Morrison, Gullick, Lawrence, Dennis, Marsh, Fletcher and Sharpe.

Citation: Sarfas C, White AD, Sibley L, Morrison AL, Gullick J,
Lawrence S, Dennis MJ, Marsh PD, Fletcher HA and Sharpe SA (2021) Characterization of the Infant Immune System and the
Influence and Immunogenicity of BCG Vaccination in Infant and Adult Rhesus Macaques. Front. Immunol. 12:754589.

DOI: 10.3389/fimmu.2021.754589

Keywords

  • BCG
  • age comparison
  • immunology
  • infant
  • infant vaccination
  • macaque

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