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Clin Vaccine Immunol. 2017 Jan 5;24(1). pii: e00360-16. doi: 10.1128/CVI.00360-16. Print 2017 Jan.

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.

Author information

1
Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
2
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
3
Albert Einstein College of Medicine, New York, New York, USA.
4
Rutgers New Jersey Medical School, Newark, New Jersey, USA.
5
Lineberger Cancer Center and Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina, USA.
6
Gillings School of Global Public Health and Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina, USA.
7
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
8
California National Primate Research Center, University of California, Davis, Davis, California, USA.
9
Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA abelk@med.unc.edu.

Abstract

Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants.

KEYWORDS:

immune activation; myeloid cells; pediatric HIV/SIV; vaccine

Comment in

PMID:
27655885
PMCID:
PMC5216431
DOI:
10.1128/CVI.00360-16
[Indexed for MEDLINE]
Free PMC Article

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