Transient Immune Activation in BCG-Vaccinated Infant Rhesus Macaques Is Not Sufficient to Influence Oral Simian Immunodeficiency Virus Infection

Wood, Matthew P.; Wood, Lianna; Templeton, Megan; Fisher, Bridget S.; Lippy, Adriana; Jones, Chloe; Arlehamn, Cecilia S. Lindestam; Sette, Alessandro; Fuller, James T.; Murapa, Patience; Jaspan, Heather B.; Fuller, Deborah H.; Sodora, Donald L.

doi:10.1093/infdis/jiz382

Cited by 13 publications

(18 citation statements)

References 31 publications

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“…36 This original pool, named "MTB300", and versions thereof have been used by a number of studies to measure and phenotype Mtb-specific responses. 28,[37][38][39][40][41][42][43][44][45][46][47][48][49][50] Due to the overlap of epitopes recognized by different species MHC this pool has also been shown to capture T cell reactivity in mice and nonhuman primates. 38,41,44,49,50 These studies have contributed to our understanding of immunity against Mtb and other mycobacteria.…”

Section: Epitope Meg Ap Ool S a S A Univer Sal Tool For Me A Suring CD 4 T Cell Re S P On S E Smentioning

confidence: 99%

Classical CD4 T cells as the cornerstone of antimycobacterial immunity

Morgan

Muskat

Tippalagama

et al. 2021

Immunological Reviews

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The goal of the End TB Strategy is to reduce TB deaths by 90% and TB incidence of new cases per year by 80% by year 2030, compared with 2015. 1 The ambitious goal of a fast deceleration of disease incidence could be achieved by a multipronged approach including increases in access to TB medical care, addressing socioeconomic factors, as well as research and technological breakthroughs especially in diagnostics, therapeutics, and vaccines. Despite significant worldwide control efforts over the last 20 years, the progress toward elimination of tuberculosis has slowed. The World Health Organization (WHO) estimates that approximately one-quarter of the world's population (1.7 billion total) is infected with Mtb. Mtb is responsible for 1.3 million deaths among HIV-negative individuals

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Section: Epitope Meg Ap Ool S a S A Univer Sal Tool For Me A Suring CD 4 T Cell Re S P On S E Smentioning

confidence: 99%

Classical CD4 T cells as the cornerstone of antimycobacterial immunity

Morgan

Muskat

Tippalagama

et al. 2021

Immunological Reviews

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“…One study modeled the mother-to-child HIV transmission through breastfeeding by orally inoculating young macaques with SIV after intradermal BCG vaccination. The vaccinated animals showed elevated monocyte and T cell activation before and after SIV infection, while the influence of BCG on susceptibility to SIV infection was unclear (Wood et al, 2019). Another study addressed Mtb co-infection with SIV by evaluating the safety of a recombinant attenuated Mtb strain carrying SIV components through oral or intradermal administration.…”

Section: Nhpsmentioning

confidence: 99%

“…For instance, IgG levels are high at birth, decrease after a few months, and reach adult levels by the time macaques are 3-4 years old ( Terao, 2009 ; Veazey et al, 2018 ; Shen et al, 2014 ). Upon intradermal BCG vaccination, infant macaques develop a papule ( Box 1 ) and erythema at the site of injection ( Wood et al, 2019 ), similar to humans. Further, infant macaques mount mycobacteria-specific CD4 + T cell responses that produce TNFα and IFNγ, but ultimately show variable efficacy of BCG vaccine upon Mtb challenge ( Wood et al, 2019 ; Verreck et al, 2017 ).…”

Section: Nhpsmentioning

confidence: 99%

“…Upon intradermal BCG vaccination, infant macaques develop a papule ( Box 1 ) and erythema at the site of injection ( Wood et al, 2019 ), similar to humans. Further, infant macaques mount mycobacteria-specific CD4 + T cell responses that produce TNFα and IFNγ, but ultimately show variable efficacy of BCG vaccine upon Mtb challenge ( Wood et al, 2019 ; Verreck et al, 2017 ). Different breeding backgrounds may be a confounding factor for this variable response to BCG ( Verreck et al, 2017 ).…”

Section: Nhpsmentioning

confidence: 99%

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Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models

Ramos

Lunney

Gonzalez-Juarrero

2020

Disease Models &Amp; Mechanisms

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Neonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette–Guérin (BCG) vaccine. Although BCG vaccination has variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it has a good safety profile and protects children from severe forms of TB. As such, new vaccines must work in conjunction with BCG at birth and, thus, it is essential to understand how BCG shapes the immune system during the first months of life. However, many aspects of the neonatal and infant immune response elicited by vaccination with BCG remain unknown, as only a handful of studies have followed BCG responses in infants. Furthermore, most animal models currently used to study TB vaccine candidates rely on adult-aged animals. This presents unique challenges when transitioning to human trials in neonates or infants. In this Review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We encourage the development of neonatal animal models for TB, especially the use of pigs.

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“…Phenotypic analyses of PBMC and lymph node cell populations were performed by multiparametric flow cytometry. Freshly isolated PBMC were counted and stained as previously described (64). Briefly, activation of T cells (CD3+, CD20-, CD14-), classical monocytes (HLA-DR+, CD14+, CD16-, CD20-, CD3-) and CD16+ monocytes (HLA-DR+, CD14+, CD16+, CD20-, CD3-) was assessed using gating strategies outlined in Figures S1 and S2 Plasma IFNα concentrations were measured with the Human IFN-α ELISA PRO kit (Mabtech), following the manufacturer's instructions.…”

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confidence: 99%

Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques

Wood

Jones

Lippy

et al. 2021

Preprint

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HIV-infected infants are at an increased risk of progressing rapidly to AIDS in the first weeks of life. Here, we evaluated immunological and virological parameters in 25 SIV-infected infant rhesus macaques to understand the factors influencing a rapid disease outcome. Infant macaques were infected with SIVmac251 and monitored for 10 to 17 weeks post-infection. SIV-infected infants were divided into either typical (TypP) or rapid (RP) progressor groups based on levels of plasma anti-SIV antibody levels and SIV plasma viral load (with RP infants having low SIV-specific antibodies and high viral loads). Following SIV infection, 11 out of 25 infant macaques exhibited an RP phenotype, with 5 of these succumbing to AIDS-related infections. Interestingly, the TypP and RP infants were similar in their CD4 depletion and activation of CD8 T cells as measured by the levels of HLA-DR on the cell surface. However, differences between the two groups were identified in other immune cell populations, including a failure to expand activated memory (CD21-CD27+) B cells in peripheral blood in RP infant macaques, as well as reduced levels of germinal center (GC) B cells and T follicular helper (Tfh) cells in spleens (4- and 10-weeks post-SIV). Reduced B cell proliferation in splenic germinal GCs was associated with increased SIV+ cell density and follicular type 1 interferon (IFN)-induced immune activation. Further analyses determined that at 2-weeks post SIV infection TypP infants exhibited elevated levels of the GC-inducing chemokine CXCL13 in plasma, as well as significantly lower levels of viral envelope diversity compared to RP infants. Our findings provide evidence that early viral and immunologic events following SIV infection contributes to impairment of B cells, Tfh cells and germinal center formation, ultimately impeding the development of SIV-specific antibody responses in rapidly progressing infant macaques.

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Transient Immune Activation in BCG-Vaccinated Infant Rhesus Macaques Is Not Sufficient to Influence Oral Simian Immunodeficiency Virus Infection

Cited by 13 publications

References 31 publications

Classical CD4 T cells as the cornerstone of antimycobacterial immunity

Classical CD4 T cells as the cornerstone of antimycobacterial immunity

Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models

Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques

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