scholarly journals Vaccine Development Against Tuberculosis Over the Last 140 Years: Failure as Part of Success

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefan H. E. Kaufmann

The year 2020 was shaped by the COVID-19 pandemic which killed more people than any other infectious disease in this particular year. At the same time, the development of highly efficacious COVID-19 vaccines within less than a year raises hope that this threat can be tamed in the near future. For the last 200 years, the agent of tuberculosis (TB) has been the worst killer amongst all pathogens. Although a vaccine has been available for 100 years, TB remains a substantial threat. The TB vaccine, Bacille Calmette-Guérin (BCG), has saved tens of millions of lives since its deployment. It was the best and only choice available amongst many attempts to develop efficacious vaccines and all competitors, be they subunit vaccines, viable vaccines or killed whole cell vaccines have failed. Yet, BCG is insufficient. The last decades have witnessed a reawakening of novel vaccine approaches based on deeper insights into immunity underlying TB and BCG immunization. In addition, technical advances in molecular genetics and the design of viral vectors and adjuvants have facilitated TB vaccine development. This treatise discusses firstly early TB vaccine developments leading to BCG as the sole preventive measure which stood the test of time, but failed to significantly contribute to TB control and secondly more recent attempts to develop novel vaccines are described that focus on the genetically modified BCG-based vaccine VPM1002, which has become the frontrunner amongst viable TB vaccine candidates. It is hoped that highly efficacious vaccines against TB will become available even though it remains unclear whether and when this ambition can be accomplished. None the less it is clear that the goal of reducing TB morbidity and mortality by 90% or 95%, respectively, by 2030 as proposed by the World Health Organization depends significantly on better vaccines.

2021 ◽  
Vol 8 ◽  
Author(s):  
Pobitra Borah ◽  
Pran Kishore Deb ◽  
Nizar A. Al-Shar’i ◽  
Lina A. Dahabiyeh ◽  
Katharigatta N. Venugopala ◽  
...  

With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.


2022 ◽  
Vol 22 ◽  
Author(s):  
Roghayyeh Baghban ◽  
Shirin Mahmoodi

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected millions of people globally, in this regard, known as a pandemic by the World Health Organization (WHO). There is sufficient scientific evidence that a preventive COVID-19 vaccine is the most effective approach to combat with COVID-19 pandemic, therefore there is an essential need for safe and protective vaccines to fight it. Methods: Global efforts in developing a vaccine against COVID-19 have resulted in the development of different vaccine platforms with various safety and efficacy including live-attenuated vaccines, inactivated vaccines, subunit vaccines, and nucleic acid-based vaccines against coronavirus disease 2019 (COVID-19). Nucleic acid-based vaccines consist of mRNA and DNA vaccines have shown promising results in stimulating cellular and humoral immune responses properly against COVID-19, which their rapid and easy manufacturing process compared to others have made them considerable. mRNA-based vaccines platform by Pfizer/BioNtech and Moderna companies are the first approved vaccines for emergency use against COVID-19. Results: This narrative review highlights the recent advances in developing nucleic acid-based vaccines for COVID-19. Conclusion: The fast global dissemination of the coronavirus has highlighted the urgent necessity to build an efficient vaccine to inhibit disease. Cooperative attempts throughout the world have paid to the fast and unprecedented production of vaccines. Much needs to be learned regarding SARSCoV-2 and vaccine development against it.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1292
Author(s):  
Noam Ben-Zuk ◽  
Ido-David Dechtman ◽  
Itai Henn ◽  
Libby Weiss ◽  
Amichay Afriat ◽  
...  

The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus Disease 2019 (COVID-19), which can vary in severity, from asymptomatic or mild disease (the vast majority of the cases) to respiratory failure, multi-organ failure, and death. Recently, several vaccines were approved for emergency use against SARS-CoV-2. However, their worldwide availability is acutely limited, and therefore, SARS-CoV-2 is still expected to cause significant morbidity and mortality in the upcoming year. Hence, additional countermeasures are needed, particularly pharmaceutical drugs that are widely accessible, safe, scalable, and affordable. In this comprehensive review, we target the prophylactic arena, focusing on small-molecule candidates. In order to consolidate a potential list of such medications, which were categorized as either antivirals, repurposed drugs, or miscellaneous, a thorough screening for relevant clinical trials was conducted. A brief molecular and/or clinical background is provided for each potential drug, rationalizing its prophylactic use as an antiviral or inflammatory modulator. Drug safety profiles are discussed, and current medical indications and research status regarding their relevance to COVID-19 are shortly reviewed. In the near future, a significant body of information regarding the effectiveness of drugs being clinically studied for COVID-19 is expected to accumulate, in addition to information regarding the efficacy of prophylactic treatments.


Author(s):  
Anupama M. Gudadappanavar ◽  
Jyoti Benni

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.


Vaccine ◽  
2016 ◽  
Vol 34 (26) ◽  
pp. 2863-2864 ◽  
Author(s):  
Birgitte K. Giersing ◽  
Kayvon Modjarrad ◽  
David C. Kaslow ◽  
Jean-Marie Okwo-Bele ◽  
Vasee S. Moorthy

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 945
Author(s):  
Saman Zafar ◽  
Muhammad Sohail Arshad ◽  
Sameen Fatima ◽  
Amna Ali ◽  
Aliyah Zaman ◽  
...  

SARS-CoV-2 has affected people from all age groups, races and ethnicities. Given that many infected individuals are asymptomatic, they transmit the disease to others unknowingly, which has resulted in the spread of infection at an alarming rate. This review aims to provide an overview of the pathophysiology, preventive measures to reduce the disease spread, therapies currently in use, an update on vaccine development and opportunities for vaccine delivery. The World Health Organization has advised several precautions including social distancing, hand washing and the use of PPE including gloves and face masks for minimizing the spread of SARS-CoV-2 infection. At present, several antiviral therapies previously approved for other infections are being repositioned to study their efficacy against SARS-CoV-2. In addition, some medicines (i.e., remdesivir, chloroquine, hydroxychloroquine) have received emergency use authorisation from the FDA. Plasma therapy has also been authorised for emergency use for the treatment of COVID-19 on a smaller scale. However, no vaccine has been approved so far against this virus. Nevertheless, several potential vaccine targets have been reported, and development of different types of vaccines including DNA, mRNA, viral vector, inactivated, subunit and vaccine-like particles is in process. It is concluded that a suitable candidate delivered through an advanced drug delivery approach would effectively boost the immune system against this coronavirus.


2018 ◽  
Vol 12 (4) ◽  
Author(s):  
Carlos A. Herrada ◽  
Md. Alamgir Kabir ◽  
Rommel Altamirano ◽  
Waseem Asghar

The Zika virus (ZIKV) is one of the most infamous mosquito-borne flavivirus on recent memory due to its potential association with high mortality rates in fetuses, microcephaly and neurological impairments in neonates, and autoimmune disorders. The severity of the disease, as well as its fast spread over several continents, has urged the World Health Organization (WHO) to declare ZIKV a global health concern. In consequence, over the past couple of years, there has been a significant effort for the development of ZIKV diagnostic methods, vaccine development, and prevention strategies. This review focuses on the most recent aspects of ZIKV research which includes the outbreaks, genome structure, multiplication and propagation of the virus, and more importantly, the development of serological and molecular detection tools such as Zika IgM antibody capture enzyme-linked immunosorbent assay (Zika MAC-ELISA), plaque reduction neutralization test (PRNT), reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR), reverse transcription-loop mediated isothermal amplification (RT-LAMP), localized surface plasmon resonance (LSPR) biosensors, nucleic acid sequence-based amplification (NASBA), and recombinase polymerase amplification (RPA). Additionally, we discuss the limitations of currently available diagnostic methods, the potential of newly developed sensing technologies, and also provide insight into future areas of research.


Author(s):  
Vijay Ramaswamy ◽  
Jason T. Huse ◽  
Yasmin Khakoo

Cerebellar astrocytoma of childhood most commonly refers to cerebellar pilocytic astrocytoma, a World health Organization (WHO) Grade I tumor. However, on occasion cerebellar astrocytomas may demonstrate more aggressive histology including fibrillary astrocytomas, pilomyxoid astrocytomas, and rarely malignant lesions. In the near future, the diagnosis of cerebellar astrocytomas will be simplified by molecular analysis for BRAF fusions rather than a purely morphological approach. The emergence of next-generation sequencing can be expected to identify single nucleotide variations and further expand our understanding of both pilocytic astrocytomas as well as rare variants that occur in the cerebellum. Therapies targeting BRAF (B-raf protooncogene) are currently in clinical trial for adult malignancies and will eventually reach the pediatric population, allowing a targeted approach to recurrent and surgically inaccessible cases of pilocytic astrocytomas.


2020 ◽  
Vol 11 ◽  
Author(s):  
Concetta Di Natale ◽  
Sara La Manna ◽  
Ilaria De Benedictis ◽  
Paola Brandi ◽  
Daniela Marasco

At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.


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