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

Self Cite

Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV envelope (Env) protein only, (ii) poxvirus vector (modified vaccinia virus Ankara [MVA])-HIV Env prime and HIV Env boost, and (iii) coadministration of HIV Env and MVA-HIV Env at all time points. The vaccines were administered with an accelerated, 3-week-interval regimen starting at birth for early induction of highly functional HIV Env-specific antibodies. We also tested whether an extended, 6-week immunization interval using the same vaccine regimen as in the coadministration group would enhance the quality of antibody responses. We found that pediatric HIV vaccines administered at birth are effective in inducing HIV Env-specific plasma IgG. The vaccine regimen consisting of only HIV Env protein induced the highest levels of variable region 1 and 2 (V1V2)-specific antibodies and tier 1 neutralizing antibodies, whereas the extended-interval regimen induced both persistent Env-specific systemic IgG and mucosal IgA responses. Antibodydependent cell-mediated cytotoxicity (ADCC) antibodies in plasma were elicited by all vaccine regimens. These data suggest that infant immunizations beginning at birth are effective for the induction of functional HIV Env-specific antibodies that could potentially protect against breast milk transmission of HIV and set the stage for immunity prior to sexual debut.

Section: Methodsmentioning

confidence: 99%

Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques

Phillips

Fouda

Eudailey

et al. 2017

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“…Consistent with this idea, Jensen and colleagues hypothesize that vaccine-induced trained immunity led to increased susceptibility of infant macaques to SIV infection through enhanced activation of CD4 ϩ T cells (22). They used a replication-deficient M. tuberculosis strain (panCD, leuCD, and secA2 deletion mutant) expressing the SIV Gag and Env antigens (attenuated M. tuberculosis-simian immunodeficiency virus vaccine [AMTB-SIV]) as a dual-purpose SIV-M. tuberculosis vaccine.…”

mentioning

confidence: 60%

“…Jensen et al (22) point out that these frequencies exceeded the antigen-specific CD4 ϩ T cell responses (both SIV and TB) observed in their previous studies; thus, the comparatively elevated activation states of the CD4 ϩ T cell populations seen in this study appear to be unrelated to vaccine specificity. As indicated above, some of the highest responses after challenge were observed in the BCG-immunized animals.…”

mentioning

confidence: 71%

“…Using stored frozen samples from their previous study (plasma, lymph nodes, mucosal tissue, and PBMCs), Jensen et al (22) measured activation marker expression and cytokine production in both myeloid (monocytes and myeloid dendritic cells [mDCs]) and CD4 ϩ T cells and provided evidence for enhanced activation in the animals immunized with BCG or AMTB-SIV relative to naive controls. Peripheral blood monocytes/macrophages and CD4 ϩ T cells from nonchallenged, immunized infant macaques expressed significantly elevated levels of the activation markers CCR5 (chemokine [C-C motif] receptor 5) and CD69 relative to nonimmunized animals at 16 to 18 weeks following immunization.…”

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confidence: 99%

See 1 more Smart Citation

Trained Immunity and Susceptibility to HIV

Derrick

2017

In this issue of Clinical and Vaccine Immunology, K. Jensen et al. (Clin Vaccine Immunol 24:e00360-16, 2017, https://doi.org/10.1128/CVI.00360-16) describe a dual-purpose attenuated Mycobacterium tuberculosis-simian immunodeficiency virus vaccine (AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures to SIV to become infected relative to nonimmunized animals. The authors hypothesized that augmented susceptibility to SIV was due to activation of CD4 ϩ T cells through trained immunity. This commentary explores the possible relationship between trained immunity, enhanced CD4 T cell responses, and increased susceptibility to human immunodeficiency virus (HIV).

“…The relevance of sex as a biological variable and rigor of experimental approaches were emphasized. Important reports on these and other trending topics were published in CVI (8)(9)(10)(11)(12)(13)(14). In this rapidly expanding scientific environment, CVI remained committed to disseminating discoveries and scientific knowledge with high scholarly and editorial standards, in line with those of other ASM journals and following the tradition and excellence of the society itself.…”

Section: A Springtime For CVImentioning

confidence: 89%

The Legacy of CVI

Pasetti

Douglas

Plaeger

2017

Clinical and Vaccine Immunology (CVI) will merge with the American Society for Microbiology (ASM) open-access journal mSphere in January 2018. We commemorate this transition by exploring the history of CVI and that of its predecessor, Clinical and Diagnostic Laboratory Immunology (CDLI), and by acknowledging their contributors. Research on vaccines, clinical immunology, and clinical diagnostic immunology published through mSphere will be available without restrictions to an ever-larger audience, which will expedite progress in the field. ASM remains committed to supporting its members and the research community by facilitating the dissemination of scientific knowledge in these important areas. KEYWORDS vaccines Clinical and Vaccine Immunology (CVI) begins a new phase as it merges with the American Society of Microbiology (ASM) journal mSphere in January 2018. The time is appropriate to look at the history of the journal and its contribution to the scientific community. Most importantly, it is an opportunity to acknowledge those who have accompanied us and advanced CVI's mission: authors, editors, editorial board members, reviewers, ASM staff, ASM members, and the enduringly supportive research community, to whom we are most sincerely grateful. Clinical and Diagnostic Laboratory ImmunologyThe journey started in January of 1994, when Clinical and Diagnostic Laboratory Immunology (CDLI) was launched (Fig. 1). During this time, the number of clinical immunology laboratories expanded due to the increased demand for immunologically based diagnostic tests for infectious diseases and clinical laboratory assessment of immune cell competency. Practices for standardization, quality control, and quality assurance matured simultaneously, along with the expectation of high-quality clinical laboratory standards. As the area of diagnostic laboratory immunology expanded, the Publications Board of ASM recognized the need for a journal exclusively dedicated to clinical laboratory immunology. With Dr. Steven D. Douglas as founding editor in chief (1994 to 2003), CDLI was established to facilitate dissemination of the growing body of research in the field (1). Indeed, the following decade witnessed major scientific advances in cellular immunology, molecular genetics, and immunodiagnostics. Diagnostic immunology evolved from the identification of antibodies resulting from infection to a variety of new assays using polyclonal and monoclonal antibodies to detect microbial antigens in body fluids and more-sophisticated methods for detecting antigen expression in tissue (2). Remarkable progress was also made in cellular immunology, particularly in the areas of immune deficiency, autoimmunity, inflammatory diseases, and immunopathogenesis. In vitro alternatives to skin testing for tuberculosis were developed, and flow cytometry and other methods for assessing immune function were increasingly utilized. These breakthroughs led to laboratory automation in diagnostic immunology (3). A series of commentaries by Isenberg, Rose, Fahey,...