scholarly journals Progress and challenges in TB vaccine development

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 199 ◽  
Author(s):  
Gerald Voss ◽  
Danilo Casimiro ◽  
Olivier Neyrolles ◽  
Ann Williams ◽  
Stefan H.E. Kaufmann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Scientific Progress ◽  
Human Infection ◽  
Experimental Medicine ◽  
Vaccine Platform ◽  
Vaccine Candidates ◽  
Clinical Endpoints ◽  
Immune Correlates ◽  
Efficacy Trials

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

scholarly journals A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1371
Author(s):  
Priscila M. S. Castanha ◽  
Ernesto T. A. Marques
Keyword(s):  
Clinical Trials ◽  
Clinical Efficacy ◽  
Vaccine Development ◽  
Global Scale ◽  
Causal Link ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Nucleic Acid Vaccines ◽  
Future Challenges ◽  
Potential Vaccine

The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a safe and effective Zika vaccine. Multiple vaccine platforms, including purified inactivated virus, nucleic acid vaccines, live-attenuated vaccines, and viral-vectored vaccines, have advanced to human clinical trials. In this review, we discuss the recent advances in the field of Zika vaccine development and the challenges for future clinical efficacy trials. We provide a brief overview on Zika vaccine platforms in the pipeline before summarizing the vaccine candidates in clinical trials, with a focus on recent, promising results from vaccine candidates that completed phase I trials. Despite low levels of transmission during recent years, ZIKV has become endemic in the Americas and the potential of large Zika outbreaks remains real. It is important for vaccine developers to continue developing their Zika vaccines, so that a potential vaccine is ready for deployment and clinical efficacy trials when the next ZIKV outbreak occurs.

scholarly journals Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview

2019 ◽  
Vol 69 (Supplement_8) ◽  
pp. S577-S579 ◽  
Author(s):  
Calman A MacLennan ◽  
Anastazia Older Aguilar ◽  
A Duncan Steele
Keyword(s):  
Best Practices ◽  
Vaccine Development ◽  
Disease Process ◽  
The United States ◽  
Human Infection ◽  
Infection Model ◽  
Infectious Agents ◽  
Vaccine Candidates ◽  
Infection Models ◽  
Consensus Report

Abstract In recent years, controlled human infection models (CHIMs) have become available for a range of infectious agents and have proved invaluable for understanding the disease process, pathogenesis, and mechanisms of immunity. CHIM studies have also contributed significantly to advancing development of a number of vaccines by providing an indication of vaccine efficacy. The Shigella CHIM has been established in 3 sites in the United States, and it is likely that the CHIM will play an important regulatory role for advancing the range of Shigella vaccine candidates that are currently in development. This supplement describes the harmonization of best practices across sites, with a view to maximizing the contribution that CHIM studies can make to Shigella vaccine development.

scholarly journals Review of Current Vaccine Development Strategies to Prevent Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Vol 48 (7) ◽  
pp. 800-809 ◽  
Author(s):  
Bindu M. Bennet ◽  
Jayanthi Wolf ◽  
Rodrigo Laureano ◽  
Rani S. Sellers
Keyword(s):  
Clinical Trials ◽  
Scientific Community ◽  
Safety Assessment ◽  
Vaccine Development ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Clinical Safety ◽  
Safety And Efficacy ◽  
Vaccine Candidates ◽  
Current Vaccine

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unparalleled efforts are ongoing to develop vaccines and treatments. Toxicologists and pathologists are involved in these efforts to test the efficacy and safety of vaccine candidates. Presently, there are several SARS-CoV-2 vaccines in clinical trials, and the pace of vaccine development has been highly accelerated to meet the urgent need. By 2021, efficacy and safety data from clinical trials are expected, and potentially a vaccine will be available for those most at risk. This review focuses on the ongoing SARS-CoV-2 vaccine development efforts with emphasis on the nonclinical safety assessment and discusses emerging preliminary data from nonclinical and clinical studies. It also provides a brief overview on vaccines for other coronaviruses, since experience gained from these can be useful in the development of SARS-CoV-2 vaccines. This review will also explain why, despite this unprecedented pace of vaccine development, rigorous standards are in place to ensure nonclinical and clinical safety and efficacy. [Box: see text]

scholarly journals Sex Differences in Immunity: Implications for the Development of Novel Vaccines Against Emerging Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Anahita Fathi ◽  
Marylyn M. Addo ◽  
Christine Dahlke
Keyword(s):  
Clinical Trials ◽  
Sex Differences ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Virus Disease ◽  
Emerging Infectious Diseases ◽  
Vaccine Safety ◽  
Emerging Infections ◽  
Emerging Pathogens ◽  
Vaccine Candidates

Vaccines are one of the greatest public health achievements and have saved millions of lives. They represent a key countermeasure to limit epidemics caused by emerging infectious diseases. The Ebola virus disease crisis in West Africa dramatically revealed the need for a rapid and strategic development of vaccines to effectively control outbreaks. Seven years later, in light of the SARS-CoV-2 pandemic, this need has never been as urgent as it is today. Vaccine development and implementation of clinical trials have been greatly accelerated, but still lack strategic design and evaluation. Responses to vaccination can vary widely across individuals based on factors like age, microbiome, co-morbidities and sex. The latter aspect has received more and more attention in recent years and a growing body of data provide evidence that sex-specific effects may lead to different outcomes of vaccine safety and efficacy. As these differences might have a significant impact on the resulting optimal vaccine regimen, sex-based differences should already be considered and investigated in pre-clinical and clinical trials. In this Review, we will highlight the clinical observations of sex-specific differences in response to vaccination, delineate sex differences in immune mechanisms, and will discuss the possible resulting implications for development of vaccine candidates against emerging infections. As multiple vaccine candidates against COVID-19 that target the same antigen are tested, vaccine development may undergo a decisive change, since we now have the opportunity to better understand mechanisms that influence vaccine-induced reactogenicity and effectiveness of different vaccines.

scholarly journals Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis

2017 ◽  
Vol 24 (7) ◽  
Author(s):  
Malcolm S. Duthie ◽  
Steven G. Reed
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Antigen Expression ◽  
Experimental Models ◽  
Vaccine Platform ◽  
Content Type ◽  
Vaccine Candidates

ABSTRACT From experimental models and the analyses of patients, it is well documented that antigen-specific T cells are critical for protection against Leishmania infection. Effective vaccines require both targeting to the pathogen and an immune stimulant to induce maturation of appropriate immune responses. While a great number of antigens have been examined as vaccine candidates against various Leishmania species, few have advanced to human or canine clinical trials. With emphasis on antigen expression, in this minireview we discuss some of the vaccine platforms that are currently being explored for the development of Leishmania vaccines. It is clear that the vaccine platform of choice can have a significant impact upon the level of protection induced by particular antigens, and we provide and highlight some examples for which the vaccine system used has impacted the protective efficacy imparted.

scholarly journals Tuberculosis Vaccine Development: Progress in Clinical Evaluation

2019 ◽  
Vol 33 (1) ◽  
Author(s):  
Suraj B. Sable ◽  
James E. Posey ◽  
Thomas J. Scriba
Keyword(s):  
Clinical Trials ◽  
Clinical Evaluation ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
Natural Immunity ◽  
Content Type ◽  
Vaccine Candidates ◽  
Current Vaccine ◽  
Development Trajectory ◽  
Airborne Disease

SUMMARY Tuberculosis (TB) is the leading killer among all infectious diseases worldwide despite extensive use of the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine. A safer and more effective vaccine than BCG is urgently required. More than a dozen TB vaccine candidates are under active evaluation in clinical trials aimed to prevent infection, disease, and recurrence. After decades of extensive research, renewed promise of an effective vaccine against this ancient airborne disease has recently emerged. In two innovative phase 2b vaccine clinical trials, one for the prevention of Mycobacterium tuberculosis infection in healthy adolescents and another for the prevention of TB disease in M. tuberculosis-infected adults, efficacy signals were observed. These breakthroughs, based on the greatly expanded knowledge of the M. tuberculosis infection spectrum, immunology of TB, and vaccine platforms, have reinvigorated the TB vaccine field. Here, we review our current understanding of natural immunity to TB, limitations in BCG immunity that are guiding vaccinologists to design novel TB vaccine candidates and concepts, and the desired attributes of a modern TB vaccine. We provide an overview of the progress of TB vaccine candidates in clinical evaluation, perspectives on the challenges faced by current vaccine concepts, and potential avenues to build on recent successes and accelerate the TB vaccine research-and-development trajectory.

scholarly journals Immunological surrogate endpoints of COVID-2019 vaccines: the evidence we have versus the evidence we need

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Pengfei Jin ◽  
Jingxin Li ◽  
Hongxing Pan ◽  
Yanfei Wu ◽  
Fengcai Zhu
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Surrogate Endpoints ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Efficacy Trials ◽  
Review Current

AbstractIn response to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, over 200 vaccine candidates against coronavirus disease 2019 (COVID-2019) are under development and currently moving forward at an unparalleled speed. The availability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates, which is crucial to control COVID-19 pandemic. Several phase 3 efficacy trials of COVID-19 vaccine candidates are under way, which provide opportunities for the determination of COVID-19 correlates of protection. In this paper, we review current knowledge for existence of COVID-19 correlates of protection, methods for assessment of immune correlates of protection and issues related to COVID-19 correlates of protection.

scholarly journals Accelerated Development of COVID-19 Vaccines: Technology Platforms, Benefits, and Associated Risks

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 747
Author(s):  
Ralf Wagner ◽  
Eberhard Hildt ◽  
Elena Grabski ◽  
Yuansheng Sun ◽  
Heidi Meyer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Phase 1 ◽  
Respiratory Illness ◽  
Dose Finding ◽  
Efficacy Evaluation ◽  
Safety And Efficacy ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
Technology Platforms

Multiple preventive COVID-19 vaccines have been developed during the ongoing SARS coronavirus (CoV) 2 pandemic, utilizing a variety of technology platforms, which have different properties, advantages, and disadvantages. The acceleration in vaccine development required to combat the current pandemic is not at the expense of the necessary regulatory requirements, including robust and comprehensive data collection along with clinical product safety and efficacy evaluation. Due to the previous development of vaccine candidates against the related highly pathogenic coronaviruses SARS-CoV and MERS-CoV, the antigen that elicits immune protection is known: the surface spike protein of SARS-CoV-2 or specific domains encoded in that protein, e.g., the receptor binding domain. From a scientific point of view and in accordance with legal frameworks and regulatory practices, for the approval of a clinic trial, the Paul-Ehrlich-Institut requires preclinical testing of vaccine candidates, including general pharmacology and toxicology as well as immunogenicity. For COVID-19 vaccine candidates, based on existing platform technologies with a sufficiently broad data base, pharmacological–toxicological testing in the case of repeated administration, quantifying systemic distribution, and proof of vaccination protection in animal models can be carried out in parallel to phase 1 or 1/2 clinical trials. To reduce the theoretical risk of an increased respiratory illness through infection-enhancing antibodies or as a result of Th2 polarization and altered cytokine profiles of the immune response following vaccination, which are of specific concern for COVID-19 vaccines, appropriate investigative testing is imperative. In general, phase 1 (vaccine safety) and 2 (dose finding, vaccination schedule) clinical trials can be combined, and combined phase 2/3 trials are recommended to determine safety and efficacy. By applying these fundamental requirements not only for the approval and analysis of clinical trials but also for the regulatory evaluation during the assessment of marketing authorization applications, several efficacious and safe COVID-19 vaccines have been licensed in the EU by unprecedentedly fast and flexible procedures. Procedural and regulatory–scientific aspects of the COVID-19 licensing processes are described in this review.

scholarly journals Overcoming Hurdles to Development of a Vaccine against Pneumocystis jirovecii

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Beth A. Garvy
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Host Range ◽  
Animal Studies ◽  
Vaccine Development ◽  
Pneumocystis Jirovecii ◽  
Content Type ◽  
Vaccine Candidates ◽  
Windows Of Opportunity

ABSTRACT Development of Pneumocystis pneumonia (PCP) is a common problem among immunosuppressed individuals. There are windows of opportunity in which vaccination would be beneficial, but to date, no vaccines have made it to clinical trials. Significant hurdles to vaccine development include host range specificity, making it difficult to translate from animal models to humans. Discovery of cross-reactive epitopes is critical to moving vaccine candidates from preclinical animal studies to clinical trials.

scholarly journals Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2

2021 ◽  
Author(s):  
Lisa Tostanoski ◽  
Lisa Gralinski ◽  
David Martinez ◽  
Alexandra Schaefer ◽  
Shant Mahrokhian ◽  
...  
Keyword(s):  
Viral Replication ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Rapid Development ◽  
Model Systems ◽  
Wild Type ◽  
Challenge Virus ◽  
Vaccine Candidates ◽  
Immune Correlates ◽  
Adenovirus Vectors

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice.

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