scholarly journals COVID-19 Vaccines Currently under Preclinical and Clinical Studies, and Associated Antiviral Immune Response

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 649 ◽  
Author(s):  
Swati Jain ◽  
Himanshu Batra ◽  
Poonam Yadav ◽  
Subhash Chand

With a death toll of over one million worldwide, the COVID-19 pandemic caused by SARS-CoV-2 has become the most devastating humanitarian catastrophe in recent decades. The fear of acquiring infection and spreading to vulnerable people has severely impacted society’s socio-economic status. To put an end to this growing number of infections and deaths as well as to switch from restricted to everyday living, an effective vaccine is desperately needed. As a result, enormous efforts have been made globally to develop numerous vaccine candidates in a matter of months. Currently, over 30 vaccine candidates are under assessment in clinical trials, with several undergoing preclinical studies. Here, we reviewed the major vaccine candidates based on the specific vaccine platform utilized to develop them. We also discussed the immune responses generated by these candidates in humans and preclinical models to determine vaccine safety, immunogenicity, and efficacy. Finally, immune responses induced in recovered COVID-19 patients and their possible vaccine development implications were also briefly reviewed.

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1027
Author(s):  
Eric A. Toth ◽  
Andrezza Chagas ◽  
Brian G. Pierce ◽  
Thomas R. Fuerst

An effective vaccine for the hepatitis C virus (HCV) is a major unmet medical and public health need, and it requires an antigen that elicits immune responses to multiple key conserved epitopes. Decades of research have generated a number of vaccine candidates; based on these data and research through clinical development, a vaccine antigen based on the E1E2 glycoprotein complex appears to be the best choice. One bottleneck in the development of an E1E2-based vaccine is that the antigen is challenging to produce in large quantities and at high levels of purity and antigenic/functional integrity. This review describes the production and characterization of E1E2-based vaccine antigens, both membrane-associated and a novel secreted form of E1E2, with a particular emphasis on the major challenges facing the field and how those challenges can be addressed.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado

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.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 199 ◽  
Author(s):  
Gerald Voss ◽  
Danilo Casimiro ◽  
Olivier Neyrolles ◽  
Ann Williams ◽  
Stefan H.E. Kaufmann ◽  
...  

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.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1409
Author(s):  
Wasim A. Prates-Syed ◽  
Lorena C. S. Chaves ◽  
Karin P. Crema ◽  
Larissa Vuitika ◽  
Aline Lira ◽  
...  

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology.


Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.


1998 ◽  
Vol 10 (8) ◽  
pp. 651 ◽  
Author(s):  
Stephen J. Kent ◽  
Ian M. Lewis

There is an urgent need for a safe and effective vaccine to prevent human immunodeficiency virus (HIV) infection. Several HIV vaccine candidates have shown promise, but many concerns regarding the safety and efficacy of current vaccines remain. A major hindrance in HIV vaccine development is a poor understanding of precisely what functions HIV vaccines are required to perform in order to protect humans from HIV-1. Only higher primates (i.e. macaques, chimpanzees and humans) are susceptible to HIV-1 or the closely related virus ‘simian immunodeficiency virus’. These species are outbred and there are remarkable genetic differences in both the immune responses to vaccines and their susceptibility to infection. The development of genetically identical macaques would be a major step towards dissecting what immune responses are required to protect from HIV infection. For example, live attenuated HIV-1 vaccines are likely to be highly efficacious, but will induce disease in a substantial proportion of recipients. Defining why a live attenuated vaccine is effective should allow safer vaccines to be developed, retaining only the immunologic properties of an effective vaccine. The reduction in ‘background genetic noise’ obtained by studying genetically identical primates would provide concise answers to critical HIV vaccine issues, by studying a minimal number of animals. Such an approach could potentially be employed in other diseases where non-human primates are the only available model. Small studies can be performed where identical twins are generated by embryo bisection; however, larger studies where multiple immune parameters are simultaneously evaluated would be facilitated by cloning technology. Despite the technical difficulties to be overcome, the potential gains in human health from the development of genetically identical non-human primates are worthy of careful consideration.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S392-S392
Author(s):  
Steven S Spires ◽  
Rebecca Rayburn-Reeves ◽  
Elizabeth Dodds Ashley ◽  
Jenna Clark ◽  
Avani P Desai ◽  
...  

Abstract Background The COVID-19 pandemic has brought vaccination to the forefront of discourse on public health. The rapid speed of COVID-19 vaccine development, utilization of novel technology, and an atmosphere of politicized misinformation have created a perfect storm for vaccine hesitancy. As early adopters of vaccination, HCWs set an example for the general population; as trusted sources of medical information, they educate and inform. However, comparatively little work has investigated HCWs' attitudes toward vaccination and how those attitudes drive their recommendation behavior. Methods We surveyed hospital employees about their personal reasons for hesitancy and beliefs about patient hesitancies and randomly assigned them to see one of three messages aimed at increasing vaccine confidence. Message themes included an appeal to return to normal life (Normalcy), a risk comparison between vaccinating or not (SDT), and an explanation of the speed of safe and effective vaccine development (Process). Results Of the 674 NC hospital employees who completed our survey in February 2021, 98% had been offered the COVID-19 vaccine, and 80% had already accepted. For the 20% who had not received the vaccine, the top reasons for hesitancy involved the speed of development and testing, and concerns of vaccine safety and effectiveness. We also found differences in susceptibility to misinformation and vaccine hesitancy across political affiliation, which was higher in Republicans compared to Democrats. HCWs were generally very comfortable recommending the COVID-19 vaccine to patients and supported the idea of sharing the message they read. Although the risk comparison message was most trusted personally, the process message was rated as both the most helpful to patients and the most likely to be shared with them (see Figure 1). This suggests that what is most appealing on a personal level is not necessarily what a HCW would recommend to their patients. Rating of personal opinions of the passages. On a scale from 1 to 7 with 1 = Strongly Disagree and 7 = Strongly Agree. This chart shows the average message ratings across the board when answering whether they thought the passages were understandable, helpful, correct, believable, and trustworthy. (Error bars are 95% CI) There was no significant difference across the messages. The Process message is seen as most helpful and is most likely to be shared with patient than the other messages On left, the average answer on a scale from 1 to 5 for “Do you think the passage you just read would help your patients feel more comfortable about getting the vaccine?” and on right, the average answer for “Would you share this passage with your patients?” Conclusion HCWs' high uptake and minimal hesitancy in recommending the COVID-19 vaccine is encouraging and merits further exploration for how to increase confidence in HCW who are hesitant to discuss and recommend vaccines to patients, as several highlighted the importance of respecting patient autonomy. Disclosures Rebecca Rayburn-Reeves, PhD, Centene Corporation (Grant/Research Support, Research Grant or Support) Jenna Clark, PhD, Centene Corporation (Grant/Research Support, Research Grant or Support) Jan Lindemans, PhD, Centene Corportation (Grant/Research Support, Scientific Research Study Investigator)


Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 195 ◽  
Author(s):  
Samia Zeb ◽  
Amjad Ali ◽  
Sardar Muhammad Gulfam ◽  
Habib Bokhari

Background and Objective: Vibrio cholerae continues to emerge as a dangerous pathogen because of increasing resistance to a number of antibiotics. This paper provides a solution to emerging antibiotic resistance by introducing novel proteins as vaccine candidates against cholera. Materials and Methods: Vibrio cholerae genome versatility is a hurdle for developing a vaccine to combat diarrhoeal infection, so its core gene information was used to determine a potential vaccine candidate. Whole genome sequence data of more than 100 Vibrio cholerae strains were used simultaneously to get core genome information. The VacSol pipeline based on reverse vaccinology was selected to address the problem of safe, cheap, temperature-stable, and effective vaccine candidates which can be used for vaccine development against Vibrio cholerae. VacSol screens vaccine candidates using integrated, well-known, and robust algorithms/tools for proteome analysis. The proteomes of the pathogens were initially screened to predict homology using BLASTp. Proteomes that are non-homologous to humans are then subjected to a predictor for localization. Helicer predicts transmembrane helices for the protein. Proteins failing to comply with the set parameters were filtered at each step, and finally, 11 proteins were filtered as vaccine candidates. Results: This selected group of vaccine candidates consists of proteins from almost all structural parts of Vibrio cholerae. Their blast results show that this filtered group includes flagellin A protein, a protein from the Zn transporter system, a lipocarrier outer membrane protein, a peptidoglycan-associated protein, a DNA-binding protein, a chemotaxis protein, a tRNA Pseuriudine synthase A, and two selected proteins, which were beta lactamases. The last two uncharacterized proteins possess 100% similarity to V. albensis and Enterobacter, respectively. Tertiary structure and active site determination show a large number of pockets on each protein. Conclusions: The most interesting finding of this study is that 10 proteins out of 11 filtered proteins are introduced as novel potential vaccine candidates. These novel vaccine candidates can result in the development of cost-effective and broad-spectrum vaccines which can be used in countries where cholera is a major contributor to diarrheal disease.


2018 ◽  
Vol 72 (1) ◽  
pp. 423-446 ◽  
Author(s):  
Heinz Feldmann ◽  
Friederike Feldmann ◽  
Andrea Marzi

The West African Ebola virus (EBOV) epidemic has fast-tracked countermeasures for this rare, emerging zoonotic pathogen. Until 2013–2014, most EBOV vaccine candidates were stalled between the preclinical and clinical milestones on the path to licensure, because of funding problems, lack of interest from pharmaceutical companies, and competing priorities in public health. The unprecedented and devastating epidemic propelled vaccine candidates toward clinical trials that were initiated near the end of the active response to the outbreak. Those trials did not have a major impact on the epidemic but provided invaluable data on vaccine safety, immunogenicity, and, to a limited degree, even efficacy in humans. There are plenty of lessons to learn from these trials, some of which are addressed in this review. Better preparation is essential to executing an effective response to EBOV in the future; yet, the first indications of waning interest are already noticeable.


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