An Overview of the Development of New Vaccines for Tuberculosis

Currently, there is only one licensed vaccine against tuberculosis (TB), the Bacillus Calmette–Guérin (BCG). Despite its protective efficacy against TB in children, BCG has failed to protect adults against pulmonary TB, lacks therapeutic value, and causes complications in immunocompromised individuals. Furthermore, it compromises the use of antigens present in the purified protein derivate of Mycobacterium tuberculosis in the diagnosis of TB. Many approaches, e.g., whole-cell organisms, subunit, and recombinant vaccines are currently being explored for safer and more efficacious TB vaccines than BCG. These approaches have been successful in developing a large number of vaccine candidates included in the TB vaccine pipeline and are at different stages of clinical trials in humans. This paper discusses current vaccination strategies, provides directions for the possible routes towards the development of new TB vaccines and highlights recent findings. The efforts for improved TB vaccines may lead to new licensed vaccines capable of replacing/supplementing BCG and conferring therapeutic value in patients with active/latent TB.

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Integrating fish models in tuberculosis vaccine development

Disease Models & Mechanisms ◽

10.1242/dmm.045716 ◽

2020 ◽

Vol 13 (8) ◽

pp. dmm045716

Author(s):

Anni K. Saralahti ◽

Meri I. E. Uusi-Mäkelä ◽

Mirja T. Niskanen ◽

Mika Rämet

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Bacillus Calmette Guerin ◽

Antibiotic Resistant ◽

Vaccine Candidates ◽

Preclinical Evaluation ◽

Vaccination Strategies ◽

Resistant Strains ◽

New Vaccines

ABSTRACTTuberculosis is a chronic infection by Mycobacterium tuberculosis that results in over 1.5 million deaths worldwide each year. Currently, there is only one vaccine against tuberculosis, the Bacillus Calmette–Guérin (BCG) vaccine. Despite widespread vaccination programmes, over 10 million new M. tuberculosis infections are diagnosed yearly, with almost half a million cases caused by antibiotic-resistant strains. Novel vaccination strategies concentrate mainly on replacing BCG or boosting its efficacy and depend on animal models that accurately recapitulate the human disease. However, efforts to produce new vaccines against an M. tuberculosis infection have encountered several challenges, including the complexity of M. tuberculosis pathogenesis and limited knowledge of the protective immune responses. The preclinical evaluation of novel tuberculosis vaccine candidates is also hampered by the lack of an appropriate animal model that could accurately predict the protective effect of vaccines in humans. Here, we review the role of zebrafish (Danio rerio) and other fish models in the development of novel vaccines against tuberculosis and discuss how these models complement the more traditional mammalian models of tuberculosis.

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Nontuberculous Mycobacteria and Heterologous Immunity to Tuberculosis

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz285 ◽

2019 ◽

Vol 220 (7) ◽

pp. 1091-1098 ◽

Cited By ~ 3

Author(s):

Javeed A Shah ◽

Cecilia S Lindestam Arlehamn ◽

David J Horne ◽

Alessandro Sette ◽

Thomas R Hawn

Keyword(s):

Nontuberculous Mycobacteria ◽

Cross Reactivity ◽

Bacillus Calmette Guerin ◽

Critical Determinant ◽

Pulmonary Tb ◽

Heterologous Immunity ◽

The World ◽

Geographic Regions ◽

New Vaccines ◽

Soil And Water

AbstractDevelopment of an improved tuberculosis (TB) vaccine is a high worldwide public health priority. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, provides variable efficacy against adult pulmonary TB, but why this protection varies is unclear. Humans are regularly exposed to non-tuberculous mycobacteria (NTM) that live in soil and water reservoirs and vary in different geographic regions around the world. Immunologic cross-reactivity may explain disparate outcomes of BCG vaccination and susceptibility to TB disease. Evidence supporting this hypothesis is increasing but challenging to obtain due to a lack of reliable research tools. In this review, we describe the progress and bottlenecks in research on NTM epidemiology, immunology and heterologous immunity to Mtb. With ongoing efforts to develop new vaccines for TB, understanding the effect of NTM on vaccine efficacy may be a critical determinant of success.

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BCG Vaccination in HIV-Infected Children

Tuberculosis Research and Treatment ◽

10.1155/2011/712736 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 10

Author(s):

James J. C. Nuttall ◽

Brian S. Eley

Keyword(s):

High Risk ◽

Young Children ◽

Protective Efficacy ◽

Bacillus Calmette Guerin ◽

Paper Briefly ◽

Safety And Efficacy ◽

Bcg Vaccination ◽

Vaccination Strategies ◽

Policy Shifts ◽

Infants And Young Children

Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies.

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Novel Vaccine Candidates against Tuberculosis

Current Medicinal Chemistry ◽

10.2174/0929867326666181126112124 ◽

2020 ◽

Vol 27 (31) ◽

pp. 5095-5118 ◽

Cited By ~ 1

Author(s):

Zhihao Li ◽

Changping Zheng ◽

Marco Terreni ◽

Lisa Tanzi ◽

Matthieu Sollogoub ◽

...

Keyword(s):

Drug Resistance ◽

Clinical Trials ◽

Recent Progress ◽

Multi Drug Resistance ◽

System Response ◽

Bacillus Calmette Guerin ◽

Vaccine Research ◽

Vaccine Candidates ◽

Immune System Response ◽

Extensively Drug Resistance

Ranking above AIDS, Tuberculosis (TB) is the ninth leading cause of death affecting and killing many individuals every year. Drugs’ efficacy is limited by a series of problems such as Multi- Drug Resistance (MDR) and Extensively-Drug Resistance (XDR). Meanwhile, the only licensed vaccine BCG (Bacillus Calmette-Guérin) existing for over 90 years is not effective enough. Consequently, it is essential to develop novel vaccines for TB prevention and immunotherapy. This paper provides an overall review of the TB prevalence, immune system response against TB and recent progress of TB vaccine research and development. Several vaccines in clinical trials are described as well as LAM-based candidates.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00108-17 ◽

2017 ◽

Vol 24 (7) ◽

Cited By ~ 9

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.

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Perspectives on New Vaccines against Arboviruses Using Insect-Specific Viruses as Platforms

Vaccines ◽

10.3390/vaccines9030263 ◽

2021 ◽

Vol 9 (3) ◽

pp. 263

Author(s):

Valéria L. Carvalho ◽

Maureen T. Long

Keyword(s):

Clinical Trials ◽

Current Status ◽

Wild Type ◽

New Locations ◽

The Creation ◽

New Vaccines

Arthropod-borne viruses (arboviruses) are global pathogens circulating endemically with local explosive outbreaks and constant encroachment into new locations. Few vaccines against arboviruses exist; most for humans are in development or clinical trials. Insect-specific viruses (ISVs) offer a unique platform for expression of arbovirus proteins, through the creation of ISV/arbovirus chimeras. Studies have shown promising results of these vaccines with several advantages over their wild-type counterparts. In this review, we discuss the current status of these potential vaccines using ISVs.

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Efficacy and Safety of AZD1222, BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2

Albanian Journal of Trauma and Emergency Surgery ◽

10.32391/ajtes.v5i1.178 ◽

2021 ◽

Vol 5 (1) ◽

pp. 791-796

Author(s):

Ilir Alimehmeti

Keyword(s):

Clinical Trials ◽

Diagnostic Tests ◽

Web Of Science ◽

Rapid Development ◽

Phase Iii ◽

Efficacy And Safety ◽

Vaccine Candidates ◽

Genetic Sequence ◽

Phase Iii Clinical Trials ◽

Clinical Trial Results

SARS-CoV-2, the beta coronavirus causing COVID-19, was isolated and categorizes as a novel one on January 7th, 2020 in China.[1] To date, official reports depict that SARS-CoV-2 has already infected 88.828.387 persons and caused 1.926.625 deaths worldwide.[2] On January 12th, 2020, China officials made public its genetic sequence, thus paving the way towards the research and development of diagnostic tests and vaccines. With regard to vaccination, e large number of clinical trials were designed and are currently undergoing, of which 189 are listed in ClinicalTrials.gov. [3] However, up to date, only three vaccines have published their respective phase III clinical trial results in peer-reviewed medical journals. [4-6] Vaccines are needed to reduce the morbidity and mortality associated with Covid-19, and multiple vaccine platforms as AZD1222 (AstraZeneca) [4], BNT162b2 (Pfizer/BioNTech) [5] and mRNA-1273 (Moderna) have been involved in the rapid development of vaccine candidates. Methodology: In this review, PubMed, Embase, Web of Science, Scopus, medRxiv, and bioRxiv were systematically scrutinized for peer-reviewed and preprint articles on phase III clinical trials of vaccines against SARS-CoV-2. In total, only three peer-reviewed papers fulfilling the search criteria were identified. Conclusions; All vaccine candidates should publish in peer-reviewed journals their efficacy and safety well before requesting approval to the national or international authorities…

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BioBoard

Asia-Pacific Biotech News ◽

10.1142/s0219030306000024 ◽

2006 ◽

Vol 10 (01) ◽

pp. 7-11

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Genome Sequencing ◽

Palm Oil ◽

Oral Vaccine ◽

Manufacturing Facility ◽

Flu Vaccine ◽

Pandemic Flu ◽

Set Up ◽

New Vaccines

Life Therapeutics Announces Influenza Program. Bharat Biotech to Launch New Vaccines and Set up Manufacturing Facility in Malaysia. National Institute of Advanced Industrial Science and Technology (AIST) Completes the Genome Sequencing of Rice Malt. Cuba and China Sign Biotech Accord. New Oral Vaccine Combats Common Strains of Rotavirus and Boosts the Immunity of Children. A Rising Fear—Resistance to Tamiflu. Sinovac Biotech Begins Pandemic Flu Vaccine Clinical Trials. Korean Stem Cell Scientist Apologizes for Fake Research Results. Two Ventures To Make Bio-fuels from Palm Oil. Beijing Approves Drug Using Virus To Treat Cancer. CyGenics' Subsidiary to Distribute Bird Flu Test Kits.

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Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIVmac251

Vaccine ◽

10.1016/j.vaccine.2007.09.017 ◽

2007 ◽

Vol 25 (47) ◽

pp. 8021-8035 ◽

Cited By ~ 43

Author(s):

Qifeng Zhou ◽

Rachmat Hidajat ◽

Bo Peng ◽

David Venzon ◽

M. Kristine Aldrich ◽

...

Keyword(s):

Host Range ◽

Simian Immunodeficiency Virus ◽

Comparative Evaluation ◽

Protective Efficacy ◽

Recombinant Vaccines ◽

Immunodeficiency Virus ◽

Adenovirus 5

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Progress and challenges in TB vaccine development

F1000Research ◽

10.12688/f1000research.13588.1 ◽

2018 ◽

Vol 7 ◽

pp. 199 ◽

Cited By ~ 51

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.

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