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

Kara Jensen, Myra Grace Dela Pena-Ponce, Michael Piatak, Rebecca Shoemaker, Kelli Oswald, William R. Jacobs, Glenn Fennelly, Carissa Lucero, Katie R. Mollan, Michael G. Hudgens, Angela Amedee, Pamela A. Kozlowski, Jacob D. Estes, Jeffrey D. Lifson, Koen K.A. Van Rompay, Michelle Larsen, Kristina De Paris

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Article numbere00360
JournalClinical and Vaccine Immunology
Volume24
Issue number1
DOIs
StatePublished - Jan 2017

Keywords

  • Immune activation
  • Myeloid cells
  • Pediatric HIV/SIV
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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