Toward Tuberculosis Vaccine Development: Recommendations for Nonhuman Primate Study Design

Laddy, Dominick J.; Bonavia, Aurelio; Hanekom, Willem A.; Kaushal, Deepak; Williams, Ann; Roederer, Mario; Seder, Robert A.; Sharpe, Sally; Verreck, Frank A. W.; Darrah, Patricia A.

doi:10.1128/iai.00776-17

Cited by 28 publications

(24 citation statements)

References 13 publications

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“…Macaques are generally considered to be a highly representative model for modeling TB due to their physiological, pathological, and immunological similarity to humans [53][54][55][56] . In addition, the NHP model is considered the most reliable and translatable model to test for preclinical trials of vaccine candidates [57][58][59] due to its ability to get coinfected with both TB and SIV. As such they may also be highly suitable for testing new TB/HIV vaccine candidates that can protect against HIV-related TB.…”

Section: Nonhuman Primate Model For Tb/hiv Vaccine Evaluationmentioning

confidence: 99%

Vaccine strategies for the Mtb/HIV copandemic

Sharan

Kaushal

2020

npj Vaccines

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One-third of world’s population is predicted to be infected with tuberculosis (TB). The resurgence of this deadly disease has been inflamed by comorbidity with human immunodeficiency virus (HIV). The risk of TB in people living with HIV (PLWH) is 15–22 times higher than people without HIV. Development of a single vaccine to combat both diseases is an ardent but tenable ambition. Studies have focused on the induction of specific humoral and cellular immune responses against HIV-1 following recombinant BCG (rBCG) expressing HIV-1 antigens. Recent advances in the TB vaccines led to the development of promising candidates such as MTBVAC, the BCG revaccination approach, H4:IC31, H56:IC31, M72/AS01 and more recently, intravenous (IV) BCG. Modification of these vaccine candidates against TB/HIV coinfection could reveal key correlates of protection in a representative animal model. This review discusses the (i) potential TB vaccine candidates that can be exploited for use as a dual vaccine against TB/HIV copandemic (ii) progress made in the realm of TB/HIV dual vaccine candidates in small animal model, NHP model, and human clinical trials (iii) the failures and promising targets for a successful vaccine strategy while delineating the correlates of vaccine-induced protection.

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Section: Nonhuman Primate Model For Tb/hiv Vaccine Evaluationmentioning

confidence: 99%

Vaccine strategies for the Mtb/HIV copandemic

Sharan

Kaushal

2020

npj Vaccines

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“…Although it seems clear that immune responses measured in peripheral blood poorly reflect lung immunity, it is currently unknown whether even immune responses detectable in BAL or sputum samples are representative of tissue resident immunity. Here, the non-human primate model could provide invaluable insight by correlating the detection of protective responses in granulomas, lymph nodes, and lung parenchyma to those measurable in BAL (96). Furthermore, even if the essential value of animal models resides in understanding mechanistic correlates of protection at the site of infection, measurement of peripheral blood biomarkers that correlate with protective immune responses in the lung should also be prioritized to enable translation to humans and facilitate clinical development of TB vaccine candidates.…”

Section: Immune Compartmentalizationmentioning

confidence: 99%

Targeting Unconventional Host Components for Vaccination-Induced Protection Against TB

et al. 2020

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The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4 + T cell responses, thought to be important for protection against TB disease, but not known to be sufficient or critical for protection. Advances in knowledge of host responses to TB afford opportunities for developing TB vaccines that target immune components not conventionally considered. Here, we describe the potential of targeting NK cells, innate immune training, B cells and antibodies, and Th17 cells in novel TB vaccine development. We also discuss attempts to target vaccine immunity specifically to the lung, the primary disease site in humans.

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“…This harmonization and standardization effort is underway within the Collaboration for TB Vaccine Development (CTVD), led by the Bill and Melinda Gates Foundation (BMGF). CTVD recommendations regarding NHP-based study design for TB vaccine development have recently been published 121 .…”

Section: Use Of Models In Translational Tb Vaccine Researchmentioning

confidence: 99%

Research and development of new tuberculosis vaccines: a review

2019

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Tuberculosis kills more people worldwide than any other single infectious disease agent, a threat made more dire by the spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). Development of new vaccines capable of preventing TB disease and new Mtb infection are an essential component of the strategy to combat the TB epidemic. Accordingly, the WHO considers the development of new TB vaccines a major public health priority. In October 2017, the WHO convened a consultation with global leaders in the TB vaccine development field to emphasize the WHO commitment to this effort and to facilitate creative approaches to the discovery and development of TB vaccine candidates. This review summarizes the presentations at this consultation, updated with scientific literature references, and includes discussions of the public health need for a TB vaccine; the status of efforts to develop vaccines to replace or potentiate BCG in infants and develop new TB vaccines for adolescents and adults; strategies being employed to diversify vaccine platforms; and new animal models being developed to facilitate TB vaccine development. A perspective on the status of these efforts from the major funders and organizational contributors also is included. This presentation highlights the extraordinary progress being made to develop new TB vaccines and provided a clear picture of the exciting development pathways that are being explored.

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Toward Tuberculosis Vaccine Development: Recommendations for Nonhuman Primate Study Design

Cited by 28 publications

References 13 publications

Vaccine strategies for the Mtb/HIV copandemic

Vaccine strategies for the Mtb/HIV copandemic

Targeting Unconventional Host Components for Vaccination-Induced Protection Against TB

Research and development of new tuberculosis vaccines: a review

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