Lewis Schrager's research while affiliated with International AIDS Vaccine Initiative and other places
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Publications (15)
Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and...
Tuberculosis represents the leading global cause of death from an infectious agent. Controlling the tuberculosis epidemic thus represents an urgent global public health priority. Epidemiological modelling suggests that, although drug treatments for tuberculosis continue to improve, WHO timelines to control the spread of the disease require a new va...
Treating tuberculosis (TB) requires a multidrug course of treatment lasting 6 months, or longer for drug-resistant TB, which is difficult to complete and often not well tolerated. Treatment failure and recurrence after end-of-treatment can have devastating consequences, including progressive debilitation, death, the transmission of Mycobacterium tu...
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. Accord...
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. Accord...
The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 – 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Immunopathogenesis of Tuberculosis,...
The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 – 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Biomarkers and Correlates, and Huma...
The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 – 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Low-Dose NHP Challenge Models, Nove...
TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing
TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical
TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some o...
TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million
deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant
tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associate...
On July 9, 2014, Aeras and the Max Planck Institute for Infection Biology convened a workshop entitled "Whole Mycobacteria Cell TB Vaccines" at the Max Planck Institute for Infection Biology on the grounds of the Charité Hospital in Berlin, Germany, close to the laboratory where, in 1882, Robert Koch first identified Mycobacterium tuberculosis (Mtb...
On November 7, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a conference entitled "Conference on Vaccine Prevention of Sustained Mycobacterium tuberculosis Infection." The purpose of this meeting was to explore the biologic plausibility, potential public health and economic impact, and regulatory feasibility in...
On April 9, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "Developing Aerosol Vaccines for Mycobacterium tuberculosis" in Bethesda, MD. The purpose of the meeting was to explore the potential for developing aerosol vaccines capable of preventing infection with M. tuberculosis (Mtb), preventin...
Citations
... Most current vaccine candidates suffer from inability to eliminate LTBI, and the majority of TB vaccine candidates currently in clinical trials were based on antigens expressed in replicating stages [158]. These TB vaccines can prevent active TB infection but not LTBI. ...
... Whilst preventive TB vaccination aims to prevent TB disease, the purpose of therapeutic TB vaccination is to reshape host immunity in order to improve outcomes, shorten treatment duration, and/or prevent relapse by establishing long-lasting specific immunological memory (4,5). Several therapeutic TB vaccine candidates are currently in the pipeline (6), showing promising results in mice and non-human primates (7). ...
... In simple terms, the ancient BCG vaccine targets still needs to be further explored in the CRISPR era [95]. Given the many intractable problems in vaccine development [96,97], novel anti-tuberculous vaccines with improved protection and safety are desperately needed to eradicate TB by 2035. Overall, the development of new anti-TB drugs and better vaccine candidates is expected to be expedited by the CRISPR revolution and may become a viable tool for eliminating TB in the future. ...
... This vaccine provides approximately 80% protection against the meningeal and disseminated TB forms, but the protective effects of the vaccine against pulmonary TB in infants or pulmonary TB reactivation in adults remain controversial [3,4]. Although significant progress has been made toward understanding the adaptive immune response induced by varying different strains of the BCG vaccine [5,6], evidence regarding the innate response is lacking. ...
... It is hoped that these interventions will effectively control and prevent TB transmissions (Lawn and Zumla 2011). However, the only vaccine currently available for TB is Bacillus Calmette-Guerin (BCG) (Schrager et al. 2018), which is known to reduce the risk of infection by 20% and the risk of infection developing into active disease by nearly 60% (Roy et al. 2014). Despite this, BCG is not effective in fully stopping the spread of TB in populations where it is prevalent. ...
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... However, whether these vaccines will be able to elicit the sterilizing immunity required to prevent acquisition is not yet completely clear. The development of a TB vaccine is further complicated by the fact that M. tuberculosis expresses about 4,000 proteins at levels that vary with the metabolic stage, complicating antigen selection 57 . Nanomaterials that can carry multiple antigens are therefore of interest for TB vaccine development, and they are further appealing because they can provide adjuvant effects required to tune the immune response towards potentially important mechanisms such as elicitation of Th1 responses. ...
... These included 15 RCTs 16,27-40 ; one of which was a trial protocol 40 ; and 12 non-randomised interventional studies 17,[41][42][43][44][45][46][47][48][49][50][51] . Other articles of potentially of relevance, but without primary data, did not meet eligibility criteria [52][53][54][55][56][57][58][59][60][61] . Only three studies were conducted in high-burden settings as shown in Table 2 and Table 3. Table 3 (RCTs, one (18 participants) from South Africa) and Table 4 (non-randomised studies, one from Brazil (6 participants) and one from South Africa (106 participants)) describe characteristics for studies selected. ...
... Phase I trial (NCT00800670): healthy adults with any BCG status CD8 + was detected in BCG+ individuals with a peak at 2 weeks and sustained TNF-a + IL-2 + secretion Smaill et al. (2013) TB-FLU-04L A negative, single-stranded RNA virus attenuated and genetically manipulated to express TB genes Phase I study (NCT02501421): BCG vaccinated (up to 6 months before the study) healthy adults Reported CD4 + /CD8 + antigen-specific responses with a peak at 21 days Walker et al. (2016) Recombinant BCG 1. Phase I trial (NCT00749034): healthy adults (Germany), any historic BCG but not in the last 10 years 2. Phase Ib trial (NCT01113281): healthy adults (South Africa), any historic BCG but not in the last 10 years 3. Phase II trial (NCT01479972): newborn infants, BCG naïve (South Africa) ...
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... As a result of the advances in immunology and molecular biology, TB vaccine development has made substantial progress. By 2022, sixteen vaccine candidates were at different phases of clinical trials, including whole-cell bacterial vaccines, subunit vaccines, and mRNA vaccines (Fletcher & Schrager, 2016). The antigens used in those vaccines involve multiple strains of Mycobacterium and over a dozen structural or secretory proteins of Mtb, which have yielded different evaluation results in laboratory and clinical experiments. ...
... Через низьку чутливість обстеження на КСБ у випадках оральних уражень, отримані результати можуть бути неінформативними. Декілька Журнал «Перспективи та інновації науки» (Серія «Педагогіка», Серія «Психологія», Серія «Медицина») № 3(37) 2024 1134 досліджень показали низьку позитивність мазків в різних біопсіях уражень ротової порожнини, близько 7,8% [8]. Патоморфологічне дослідження зразка біопсійного матеріалу хворого на туберкульоз ротової порожнини зазвичай виявляє класичний казеозний гранулематоз з центральним некрозом, оточеним епітеліоїдними клітинами, гігантськими клітинами Лангханса та інфільтрацією лімфоцитів [9]. ...
