Jorge H. Soler

Bio: Jorge H. Soler is an academic researcher from University of Michigan. The author has contributed to research in topics: T cell & CD8. The author has an hindex of 11, co-authored 12 publications receiving 695 citations. Previous affiliations of Jorge H. Soler include Public Health Research Institute & Columbia University.

PrEP Awareness and Perceived Barriers Among Single Young Men who have Sex with Men

Abstract: Pre-exposure prophylaxis (PrEP) has the potential to help reduce new HIV infections among young men who have sex with men (YMSM). Using a cross-sectional survey of YMSM (N=1,507; ages 18-24), we gauged YMSM's PrEP awareness and PrEP-related beliefs regarding side effects, accessibility, and affordability. Overall, 27% of the sample had heard about PrEP; 1% reported ever using PrEP prior to sex. In a multivariate logistic regression, we found that YMSM were more likely to have heard about PrEP if they were older, more educated, were residentially unstable in the prior 30 days, had insurance, or reported having at least one sexually transmitted infection in their lifetime. We found no differences by race/ethnicity, history of incarceration, or recent sexual risk behavior. In multivariate linear regression models, Black and Latino YMSM were more likely than Whites to state they would not use PrEP because of side effect concerns. YMSM were more likely to indicate that they would not be able to afford PrEP if they did not have insurance or if they had a prior sexually transmitted infection, PrEP rollout may be hindered due to lack of awareness, as well as perceived barriers regarding its use. We propose strategies to maximize equity in PrEP awareness and access if it is to be scaled up among YMSM.

A New Recombinant Bacille Calmette-Guérin Vaccine Safely Induces Significantly Enhanced Tuberculosis-Specific Immunity in Human Volunteers

Abstract: One third of the world’s population is infected with M. tuberculosis, and 2 million tuberculosis (TB) deaths occur annually (http://www.who.int/gtb/publications/globrep01/index.html). These staggering statistics persist despite the availability of a TB vaccine, M. bovis Bacille Calmette Guerin (BCG), for over 75 years. New vaccines are urgently needed to reduce this immense burden of TB disease. One potential approach for improving TB vaccination is the generation of recombinant BCG (rBCG), which may work better than standard BCG strains by overexpressing key M. tuberculosis antigens, immunoenhancers and/or proteins promoting phagosomal escape and potent CD8+ T cell stimulation [1–7]. Furthermore, rBCG are attractive options because of the extensive clinical experience, known immunogenicity protective against severe TB disease, and relative safety profile of standard BCG strains. However, rBCG TB vaccines have not been studied in humans to demonstrate safety and enhanced immunogenicity of this approach. M. tuberculosis is an intracellular pathogen that replicates in host mononuclear phagocytes [8, 9]. Bacillary proteins secreted intracellularly are early targets of TB immunity [8–10]. Immunization of guinea pigs with purified M. tuberculosis extracellular proteins, including the 30 kDa major secretory protein (a mycolyltransferase known as α-antigen and antigen 85b [11, 12]), induces substantial protection against aerosol challenge with highly virulent M. tuberculosis [9]. Furthermore, M. tuberculosis secreted proteins [13] and DNA encoding secreted antigens [14] also induce TB immunity in mice. Although previous vaccinations in animals induced significant levels of protection, this protection was never superior and usually less than induced by BCG vaccination. Horwitz et al. generated recombinant BCG overexpressing the 30 kD Ag85b antigen of M. tuberculosis (rBCG30) in 2 distinct BCG strains. These rBCG30 vaccines were the first new TB vaccines capable of inducing protective immunity in guinea pigs significantly better than nonrecombinant BCG [1, 2]. Based upon these promising results, the Aeras Foundation initiated clinical development of rBCG30 as their first model TB vaccine candidate. We report the initial clinical and detailed immunological testing of rBCG30 in QuantiFERON PPD negative, adult volunteers. rBCG30 was as safe as nonrecombinant BCG and induced significantly increased Ag85b-specific immunity in multiple relevant subsets of mycobacteria-specific immune responses.

The effect of bacille Calmette-Guérin vaccine strain and route of administration on induced immune responses in vaccinated infants.

Abstract: Vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) has variable efficacy in preventing tuberculosis Both BCG strain and route of administration have been implicated in determining efficacy; however, these variables are not considered in current clinical recommendations for vaccine choice We evaluated antigen-specific immunity after percutaneous or intradermal administration of Japanese BCG or intradermal administration of Danish BCG Ten weeks after vaccination of neonates, percutaneous Japanese BCG had induced significantly higher frequencies of BCG-specific interferon- gamma -producing CD4(+) and CD8(+) T cells in BCG-stimulated whole blood than did intradermal Danish BCG Similarly, percutaneous vaccination with Japanese BCG resulted in significantly greater secretion of the T helper 1-type cytokines interferon- gamma, tumor necrosis factor- alpha , and interleukin-2; significantly lower secretion of the T helper 2-type cytokine interleukin-4; and greater CD4(+) and CD8(+) T cell proliferation Thus, BCG strain and route of neonatal vaccination confer different levels of immune activation, which may affect the efficacy of the vaccine

Bacillus Calmette Guerin Vaccination of Human Newborns Induces a Specific, Functional CD8+ T Cell Response

Abstract: Mounting evidence points to CD8+ T cells playing an important role in protective immunity against Mycobacterium tuberculosis. The only available vaccine against tuberculosis, bacillus Calmette Guerin (BCG), has traditionally been viewed not to induce these cells optimally. In this study, we show that vaccination of human newborns with BCG does indeed induce a specific CD8+ T cell response. These cells degranulated or secreted IFN-gamma, but not both, when infant blood was incubated with BCG. This stimulation also resulted in proliferation and up-regulation of cytotoxic molecules. Overall, the specific CD8+ T cell response was quantitatively smaller than the BCG-induced CD4+ T cell response. Incubation of whole blood with M. tuberculosis also caused CD8+ T cell IFN-gamma expression. We conclude that BCG induces a robust CD8+ T cell response, which may contribute to vaccination-induced protection against tuberculosis.

LGBT Community, Social Network Characteristics, and Smoking Behaviors in Young Sexual Minority Women

Abstract: Smoking rates among young sexual minority women (YSMW) are disproportionately high as compared to heterosexual populations. While this disparity has commonly been attributed to the sexual minority stress process, little empirical work has explored what may protect YSMW from high rates of smoking. Using data (N = 471) from a cross-sectional study designed to investigate YSMW's (age 18-24) smoking behaviors and correlates; we explore the relationship of LGBT community connections, YSMW's social network characteristics, and stress to smoking behaviors (i.e., status, frequency, amount). Through this analysis, we find support for LGBT community connection as well as friendships with other sexual minorities as protective in relation to YSMW's smoking behaviors. We discuss the implications of our results, highlighting the need for future longitudinal research and interventions designed to bolster YSMW's connections to the LGBT community and their social networks.

Cell-Mediated Immune Responses in Tuberculosis

Abstract: Tuberculosis is primarily a disease of the lung, and dissemination of the disease depends on productive infection of this critical organ. Upon aerosol infection with Mycobacterium tuberculosis (Mtb), the acquired cellular immune response is slow to be induced and to be expressed within the lung. This slowness allows infection to become well established; thus, the acquired response is expressed in an inflammatory site that has been initiated and modulated by the bacterium. Mtb has a variety of surface molecules that interact with the innate response, and this interaction along with the autoregulation of the immune response by several mechanisms results in less-than-optimal control of bacterial growth. To improve current vaccine strategies, we must understand the factors that mediate induction, expression, and regulation of the immune response in the lung. We must also determine how to induce both known and novel immunoprotective responses without inducing immunopathologic consequences.

Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development

Abstract: New tools for controlling tuberculosis are urgently needed. Despite our emerging understanding of the biogeography of Mycobacterium tuberculosis, the implications for development of new diagnostics, drugs, and vaccines is unknown. M tuberculosis has a clonal genetic population structure that is geographically constrained. Evidence suggests strain-specific differences in virulence and immunogenicity in light of this global phylogeography. We propose a strain selection framework, based on robust phylogenetic markers, which will allow for systematic and comprehensive evaluation of new tools for tuberculosis control.

Genome plasticity of BCG and impact on vaccine efficacy.

Abstract: To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Guerin (BCG) vaccines, Mycobacterium bovis BCG Pasteur 1173P2 has been subjected to comparative genome and transcriptome analysis. The 4,374,522-bp genome contains 3,954 protein-coding genes, 58 of which are present in two copies as a result of two independent tandem duplications, DU1 and DU2. DU1 is restricted to BCG Pasteur, although four forms of DU2 exist; DU2-I is confined to early BCG vaccines, like BCG Japan, whereas DU2-III and DU2-IV occur in the late vaccines. The glycerol-3-phosphate dehydrogenase gene, glpD2, is one of only three genes common to all four DU2 variants, implying that BCG requires higher levels of this enzyme to grow on glycerol. Further amplification of the DU2 region is ongoing, even within vaccine preparations used to immunize humans. An evolutionary scheme for BCG vaccines was established by analyzing DU2 and other markers. Lesions in genes encoding sigma-factors and pleiotropic transcriptional regulators, like PhoR and Crp, were also uncovered in various BCG strains; together with gene amplification, these affect gene expression levels, immunogenicity, and, possibly, protection against tuberculosis. Furthermore, the combined findings suggest that early BCG vaccines may even be superior to the later ones that are more widely used.

Vaccines against tuberculosis: where are we and where do we need to go?

Abstract: In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.