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 SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Rna Virus ◽  
Protein S ◽  
Effective Vaccine ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

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 Vaccines for COVID-19 - state of the art

2021 ◽  
Vol 21 (suppl 1) ◽  
pp. 13-19
Author(s):  
Eduardo Jorge da Fonseca Lima ◽  
Amalia Mapurunga Almeida ◽  
Renato de Ávila Kfouri
Keyword(s):  
Clinical Trial ◽  
Large Scale ◽  
State Of The Art ◽  
Current Knowledge ◽  
Entire Population ◽  
Ethical Aspects ◽  
Research Teams ◽  
Vaccine Candidates ◽  
New Generation

Abstract Vaccine candidates against COVID-19 have diverse compositions, from traditional inac-tivated virus vaccines to various new-generation vaccines. Currently, approximately 175 research teams worldwide are studying various vaccine possibilities as the necessityto vacci-nate the entire population against the SARS-CoV-2 virus is urgent. Although, the development of a safe and effective COVID-19 vaccine is not easy, the manufacturing, distribution, and administration of the vaccine can also face extraordinary challenges. In this review, we enhance some of the current knowledge regarding the clinical trial phases on different COVID-19 vaccine candidates, its potential strengths and disadvantages, and to discuss ethical aspects and their chances of success in large-scale applications.

scholarly journals Vaccines against COVID-19 – Catching the Rays of Hope

2021 ◽  
pp. 469-488
Author(s):  
Suresh Kumar Srinivasamurthy ◽  
Laxminarayana Kurady Bairy
Keyword(s):  
Herd Immunity ◽  
Clinical Impact ◽  
Morbidity And Mortality ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Practical Possibility ◽  
Efficacy Trials ◽  
The World ◽  
The Status ◽  
Early Phase Clinical Trials

COVID-19 pandemic has affected the world in all its dimensions. With herd immunity being a distant and non-practical possibility, vaccination remains most tractable approach to reduce morbidity and mortality. Several early phase clinical trials have proved the immunogenicity of vaccines. The efficacy trials have shown reduction in chance of acquiring COVID-19 disease after vaccination. The vaccines approved for emergency use have reported efficacy above 50% thus making them important public health tool in controlling the pandemic. Nevertheless, several questions remain elusive such as whether these approved vaccines are effective against newer variants of the virus; whether vaccination prevents transmission of the virus in the community; clinical impact of vaccination on morbidity and mortality. This review aims to elucidate the status of vaccine candidates in advanced trials along with the vaccines, which have been granted emergency approvals. Further, we collate the data on vaccines efficacy phase 3 trials and their probability of efficacy against newer variants.

scholarly journals Covid-19 vaccine trials and ethics: Protection delayed is protection denied

2020 ◽  
pp. 01-03
Author(s):  
T Jacob John ◽  
Dhanya Dharmapalan
Keyword(s):  
Large Scale ◽  
Protective Efficacy ◽  
Informed Choice ◽  
Effective Vaccine ◽  
Compassionate Use ◽  
Vaccine Research ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Risk Of Death ◽  
Vaccine Trials

Abstract The Covid-19 pandemic is raging, taking a heavy toll of lives and livelihoods. The need for safe and effective vaccine(s) is urgent. Vaccine research has progressed rapidly and a few vaccine candidates have passed trial Phases 1 and 2, confirming reasonable safety and immunogenicity parameters. They are ready for large scale Phase 3 trials to quantify protective efficacy, if any, and to detect uncommon but serious adverse effects, if any. These developments present unprecedented opportunities and challenges, scientific and ethical. Globally hundreds die every day due to Covid-19, and emergency/compassionate use of vaccine candidates that are ready for Phase 3 trials are likely to save lives. We perceive an ethical imperative to allow such vaccination for those at high risk of death who voluntarily make such an informed choice – for them protection delayed will be tantamount to protection denied.

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

2021 ◽  
Author(s):  
Lisa H. Tostanoski ◽  
Lisa E. Gralinski ◽  
David R. Martinez ◽  
Alexandra Schaefer ◽  
Shant H. Mahrokhian ◽  
...  
Keyword(s):  
Viral Replication ◽  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Adenovirus Serotype ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Antibody Titers ◽  
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. Importance We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

scholarly journals Complex immune correlates of protection in HIV-1 vaccine efficacy trials

2017 ◽  
Vol 275 (1) ◽  
pp. 245-261 ◽  
Author(s):  
Georgia D. Tomaras ◽  
Stanley A. Plotkin
Keyword(s):  
Vaccine Efficacy ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Efficacy Trials ◽  
Hiv 1

DNA Vaccines

2021 ◽  
Author(s):  
Jeffrey B Ulmer
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Large Scale ◽  
Dna Vaccines ◽  
Low Cost ◽  
Animal Health ◽  
Phase 3 ◽  
Efficacy Trials ◽  
Human Use

DNA vaccines were first discovered more than 30 years ago. Because DNA vaccines result in antigen production in situ (i.e., mimic a virus infection), they elicit broad-based immune responses, including antibodies and T cells. Induction of protective immunity has been established in scores of animal models of infectious and non-infectious diseases. Hundreds of human clinical trials have been conducted demonstrating safety and, in many cases, antigen-specific immune responses. Several animal health vaccines based on DNA have been approved and are in use. Many DNA vaccines are in various stages of human clinical testing, including a few in phase 3 efficacy trials and the recent Emergency Use Authorization of a COVID-19 vaccine, but to date no DNA vaccines have been fully licensed for human use. DNA vaccines are thermostable and amenable to large-scale manufacturing at relatively low cost, hence well-suited for global use, particularly in the developing world. If potency in humans could be achieved, DNA vaccines would have the potential to be a radical innovation that could disrupt the vaccine industry.

Actinobacillus pleuropneumoniaesurface polysaccharides: their role in diagnosis and immunogenicity

2000 ◽  
Vol 1 (2) ◽  
pp. 73-93 ◽  
Author(s):  
J. Daniel Dubreuil ◽  
Mario Jacques ◽  
Khyali R. Mittal ◽  
Marcelo Gottschalk
Keyword(s):  
Vaccine Development ◽  
Current Knowledge ◽  
Diagnostic Tools ◽  
Virulence Determinants ◽  
Animal Protection ◽  
Rtx Toxins ◽  
Crucial Information ◽  
Surface Polysaccharides ◽  
Review Current

AbstractActinobacillus pleuropneumoniaeis an important pig pathogen that is responsible for swine pleuropneumonia, a highly contagious respiratory infection. Knowledge of the importance, composition and structural determination of the major antigens involved in virulence provides crucial information that could lead to the development of a rationale for the production of specific serodiagnostic tools as well as vaccine development. Thus, efforts have been devoted to study mainlyA. pleuropneumoniaevirulence determinants with special emphasis on the Apx toxins (forA. pleuropneumoniaeRTX toxins). In comparison, little attention has been given to the surface polysaccharides, which include capsular polysaccharides (CPS) and cell-wall lipopolysaccharides (LPS). Here, we review current knowledge on CPS and LPS ofA. pleuropneumoniaeused as diagnostic tools to monitor the infection and as immunogens for inclusion in vaccine preparations for animal protection.

scholarly journals Rational Vaccine Design in Times of Emerging Diseases: The Critical Choices of Immunological Correlates of Protection, Vaccine Antigen and Immunomodulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 501
Author(s):  
Virgil Schijns ◽  
Dragomira Majhen ◽  
Peter van der Ley ◽  
Aneesh Thakur ◽  
Artur Summerfield ◽  
...  
Keyword(s):  
Rational Design ◽  
Current Knowledge ◽  
Medical Intervention ◽  
Emerging Diseases ◽  
Vaccine Antigen ◽  
Vaccine Adjuvant ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Life Threatening ◽  
Rational Vaccine Design

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. Finally we review approaches to rational antigen selection and rational vaccine adjuvant design. Harnessing current knowledge on protective immune responses in combination with critical vaccine components is imperative to the prevention of future life-threatening diseases.

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