COVID-19 Vaccine Candidates Research Articles

Hot race for COVID-19 vaccines – Light at the end of the tunnel just got brighter

While the COVID-19 pandemic continues to gallop across the world, there is plausible hope thatthe pandemic might be dead soon – thanks to rapid emergence of positive data from variousongoing clinical trials involving COVID-19 vaccine candidates.

COVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SARS-CoV-2 spike induce robust T- and B-cell immune responses and full efficacy in mice.

Vaccines against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are urgently needed. We developed two COVID-19 vaccines based on modified vaccinia virus Ankara (MVA) vectors expressing the entire SARS-CoV-2 spike (S) protein (MVA-CoV2-S); their immunogenicity was evaluated in mice using DNA/MVA or MVA/MVA prime/boost immunizations. Both vaccines induced robust, broad and polyfunctional S-specific CD4+ (mainly Th1) and CD8+ T-cell responses, with a T effector memory phenotype. DNA/MVA immunizations elicited higher T-cell responses. All vaccine regimens triggered high titers of IgG antibodies specific for the S, as well as for the receptor-binding domain; the predominance of the IgG2c isotype was indicative of Th1 immunity. Notably, serum samples from vaccinated mice neutralized SARS-CoV-2 in cell cultures, and those from MVA/MVA immunizations showed a higher neutralizing capacity. Remarkably, one or two doses of MVA-CoV2-S protect humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2. In addition, two doses of MVA-CoV2-S confer full inhibition of virus replication in the lungs. These results demonstrate the robust immunogenicity and full efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.IMPORTANCE The continuous dissemination of the novel emerging SARS-CoV-2 virus, with more than 78 million infected cases worldwide and higher than 1,700,000 deaths as of December 23, 2020, highlights the urgent need for the development of novel vaccines against COVID-19. With this aim, we have developed novel vaccine candidates based on the poxvirus modified vaccinia virus Ankara (MVA) strain expressing the full-length SARS-CoV-2 spike (S) protein, and we have evaluated their immunogenicity in mice using DNA/MVA or MVA/MVA prime/boost immunization protocols. The results showed the induction of a potent S-specific T-cell response and high titers of neutralizing antibodies. Remarkably, humanized K18-hACE2 mice immunized with one or two doses of the MVA-based vaccine were 100% protected from SARS-CoV-2 lethality. Moreover, two doses of the vaccine prevented virus replication in lungs. Our findings prove the robust immunogenicity and efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.

Covid-19 vaccine candidates under clinical evaluation - a review

Vaccine development against SARS‐CoV‐2 have reached to a centre stage across globe attributed to the Covid 19 pandemic As treatment options for Covid-19 are yet to be explored, so the onus is on vaccines to stimulate humoral and cellular immunity in fight against present pandemic In vaccinology the prior research against similar coronaviruses such as SARS and MERS have enabled the rapid development of COVID‐19 vaccine Smallpox eradication and diseases like polio, mumps and measles have been checked using vaccines Keeping in view of the current situation Scientific world has responded remarkably with development and acceleration of various vaccine candidates Present review highlights the vaccines that are under clinical evaluation stage as per the WHO report of August 2020

How world policy affects the equitable distribution of the COVID-19 vaccine

Journal of Prescribing PracticeVol. 3, No. 1 News AnalysisHow world policy affects the equitable distribution of the COVID-19 vaccineAysha MendesAysha MendesE-mail Address: [email protected]Freelance journalist specialising in health, psychology and nursingSearch for more papers by this authorAysha MendesPublished Online:11 Jan 2021https://doi.org/10.12968/jprp.2021.3.1.10AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View article References COVAX. Commitment agreements. 2020. https://www.gavi.org/sites/default/files/covid/pr/COVAX_CA_COIP_List_COVAX_PR_30-09.pdf (accessed 16 December 2020) Google ScholarBerkley S. COVAX explained. 2020. https://www.gavi.org/vaccineswork/covax-explained (accessed 16 December 2020) Google ScholarSo Anthony D, Woo Joshua. 2020 Reserving coronavirus disease 2019 vaccines for global access: cross sectional analysis. BMJ 371: m4750. https://tinyurl.com/yabppfjf (accessed 16 December 2020) Google ScholarWorld Health Organization. DRAFT landscape of COVID-19 candidate vaccines. 2020. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed 16 December 2020) Google Scholar FiguresReferencesRelatedDetails 2 January 2021Volume 3Issue 1ISSN (print): 2631-8385ISSN (online): 2631-8393 Metrics History Published online 11 January 2021 Published in print 2 January 2021 Information© MA Healthcare LimitedPDF download

An overview of COVID-19 vaccine candidates

For the past two years, people worldwide were experiencing one of the most massive pandemics, the COVID-19. It is caused by a virus that is called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which mainly attacks the respiratory system. Since there is no previous experience treating the disease, the drug development process is extremely difficult. People in dire need of vaccines were urgently needed to restore their lives to normal. As time went by, medical staff and experts spent numerous amounts of time and effort studying this virus. Nowadays, as the vaccine technology of various countries was very mature, vaccines with various technological paths have entered the experimental stage one after another. Eventually, effective vaccines are finally ready for wild inoculation for everyone by collaborating with all medical researchers. Currently, there are four kinds of COVID-19 vaccines available in different countries. They are inactivated vaccines, mRNA-based vaccines, viral vector vaccines, and recombinant vaccines. Most of these COVID-19 vaccines are in Phase 3 and provided in different countries. Those vaccines were manufactured in different countries, and their general production and technical characteristics will be discussed in the following paragraphs. The main purpose is trying to provide some fundamental and comprehensive background knowledge about currently available COVID-19 vaccines. It could be a reference list for those audiences who have not decided to take which vaccine.

Prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

ABSTRACT COVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 cells) and intracellular IFN-γ in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

Lessons Relearned? H1N1, COVID-19, and Vaccination Planning.

Lessons Relearned? H1N1, COVID-19, and Vaccination Planning.

Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against COVID-19: COVAC1, a Phase I, Dose-Ranging Trial

Summary: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0·1-10·0mg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays.Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both pConcurrent anti-S IgG ranged from GM concentration (95% CI) 74 (45-119) at 0·1mg to 1023 (468-2236) ng/ml at 5·0mg (pInterpretation: Encapsulated saRNA is safe for clinical development and is immunogenic at low dose levels. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2.Trial Registration: (ISRCTN17072692, EudraCT 2020-001646-20)Funding Statement: Medical Research Council UKRI (MC_PC_19076 and MC_UU_12023/23), National Institute for Health Research, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust.Declaration of Interests: P.F.M. and R.J.S. are co-inventors on a patent application covering this SARS-CoV-2 saRNA vaccine. All other authors have nothing to declare. Ethics Approval Statement: This study was approved in the UK by the Medicines and Healthcare products Regulatory Agency and the North East - York Research Ethics Committee (reference 20/SC/0145).

Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates

ABSTRACT COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19

ABSTRACT A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Health Silk Road 2020: A Bridge to the Future of Health for All

Health Silk Road 2020: A Bridge to the Future of Health for All

On the way to COVID-19 vaccine development: tireless efforts and outcomes

Novel corona virus disease (COVID-19), since its emergence in November 2019, took the toll of a huge number of human lives. It is a β-corona-virus also known as SARS-CoV2. The safest and most effective way to prevent the disease is definitely vaccination amongst the large population. To the best of our knowledge, more than 200 vaccine candidates for COVID-19 were developed by the scientists of research institutions and pharmaceutical companies and nearly 52 candidates were in human trials. Till now, only 15 vaccines are being offered to the general population in the world, out of which 2 vaccines are RNA, 6 are conventional inactivated, 5 viral vector and 2 protein subunit. Here, we tried to unfold the events and efforts behind the successes of new innovations of COVID-19 vaccines, the world has achieved yet.

A cost/benefit analysis of clinical trial designs for COVID-19 vaccine candidates.

We compare and contrast the expected duration and number of infections and deaths averted among several designs for clinical trials of COVID-19 vaccine candidates, including traditional and adaptive randomized clinical trials and human challenge trials. Using epidemiological models calibrated to the current pandemic, we simulate the time course of each clinical trial design for 756 unique combinations of parameters, allowing us to determine which trial design is most effective for a given scenario. A human challenge trial provides maximal net benefits-averting an additional 1.1M infections and 8,000 deaths in the U.S. compared to the next best clinical trial design-if its set-up time is short or the pandemic spreads slowly. In most of the other cases, an adaptive trial provides greater net benefits.

Comparison of the immunogenicity & protective efficacy of various SARS-CoV-2 vaccine candidates in non-human primates.

Background & objectives:The COVID-19 pandemic has emerged as a global public health crisis and research groups worldwide are engaged in developing vaccine candidates to curb its transmission, with a few vaccines having progressed to advanced stages of clinical trials. The aim of this systematic review was to compare immunogenicity and protective efficacy of various SARS-CoV-2 vaccine candidates tested in non-human primate (NHP) models.Methods:Literature on effect of SARS-CoV-2 vaccines in NHP models reported on PubMed and preprint platforms (medRxiv and bioRxiv) till October 22, 2020, was searched with the following terms: coronavirus vaccine, COVID-19 vaccine, SARS-CoV-2 vaccine, nonhuman primate, and rhesus macaque.Results:Our search yielded 19 studies, which reported immune response elicited by 18 vaccine candidates in NHP. All the vaccines induced detectable neutralizing antibody (NAb) titres in the serum of vaccinated animals, with some showing effective viral clearance from various organs. The vaccinated animals also showed nil to mild histopathological changes in their lungs compared to placebo groups in the trials that performed necropsy.Interpretation & conclusions:Our findings highlighted onset of quick immunogenicity and protective efficacy of mRNA-1273, followed by Ad26.CoV2.S, NVX-CoV2373, BNT162b2, RBD and BBV152 vaccine candidates in preclinical trials as compared to the others. NHP data also showed correlation with clinical trial data available for a few vaccines. Preclinical trials of COVID-19 vaccine candidates in NHPs yielded promising results, with some candidates faring better than others.

COVID-19 vaccines - are we there yet?

SUMMARYThe novel coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, is a highly infectious human respiratory pathogen to which the global population had no prior immunity. The virus will likely continue to cause significant morbidity until there is a broadly effective vaccineAs of mid-December 2020, more than 200 COVID-19 vaccine candidates are in development and 11 have entered phase III clinical trials globally. All generate immunity to the viral spike glycoproteinThree vaccine candidates have agreements for procurement and use in Australia if efficacy and safety requirements are met – one protein-based vaccine, one vaccine using a simian-derived adenovirus vector and one messenger RNA vaccine. The latter two vaccines have published interim analyses and efficacy results of their phase III trials. The messenger RNA vaccine is being rolled out in the UK, USA and CanadaSignificant uncertainties remain. How well will some of those at highest risk of severe disease (such as older people aged >75 years and those with immunocompromising conditions) be protected by a vaccine, and for how long? Also, to what extent will vaccination protect against infection? This will determine the degree of indirect ‘herd’ protection needed through broad vaccine coverage of younger age groups

A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

SummaryBackgroundThe spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults.MethodsHere, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice.FindingsA single vaccination generates spike-specific Th1 cells, Th1-like Foxp3+ regulatory T cells, polyfunctional spike-specific CD8+ T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice.ConclusionsThis study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons.FundingThis study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK.

COVID-19 Vaccines May Not Prevent Nasal SARS-CoV-2 Infection and Asymptomatic Transmission.

Current COVID-19 vaccine candidates are administered by injection and designed to produce an IgG response, preventing viremia and the COVID-19 syndrome. However, systemic respiratory vaccines generally provide limited protection against viral replication and shedding within the airway, as this requires a local mucosal secretory IgA response. Indeed, preclinical studies of adenovirus and mRNA candidate vaccines demonstrated persistent virus in nasal swabs despite preventing COVID-19. This suggests that systemically vaccinated patients, while asymptomatic, may still be become infected and transmit live virus from the upper airway. COVID-19 is known to spread through respiratory droplets and aerosols. Furthermore, significant evidence has shown that many clinic and surgical endonasal procedures are aerosol generating. Until further knowledge is acquired regarding mucosal immunity following systemic vaccination, otolaryngology providers should maintain precautions against viral transmission to protect the proportion of persistently vulnerable patients who exhibit subtotal vaccine efficacy or waning immunity or who defer vaccination.

Impact of COVID-19 Pandemic on the Working Structure of Research Organizations in Singapore

The global COVID-19 pandemic is exacting a terrible human toll and menacing the world economy. As proposed by the World Health Organization, there are currently over 100 COVID-19 vaccine candidates under development and some of these are in the human trial phase. However, various experts are of the view that the economic damage will affect people no less than the disease itself. In order to reduce the risk of transmission, conducting online classes and work-from-home are in trend now-a-days. Similarly, in Singapore, a number of organizations have asked their employees to work-from-home since lockdown, and people are gradually getting accustomed to such practices. Of course, this initiative would be followed by both benefits and detriments, detailed views of which are discussed. The impact of COVID-19 on the functioning of the universities and the research institutes is then studied. Finally, we highlight how these organizations can remain productive in this unprecedented situation.

Reserving coronavirus disease 2019 vaccines for global access: cross sectional analysis

ObjectiveTo analyze the premarket purchase commitments for coronavirus disease 2019 (covid-19) vaccines from leading manufacturers to recipient countries.DesignCross sectional analysis.Data sourcesWorld Health Organization’s draft landscape of covid-19 candidate vaccines, along...

SARS-CoV-2 Biochemistry, Transmission, Clinical Manifestations, and Prevention

The first human case of COVID-19, caused by the novel coronavirus, was reported by health officials in the city of Wuhan, China, in December of 2019. The virus was identified as a novel coronavirus in early January 2020, and its genetic sequence was shared publicly on January 11, 2020. The novel virus, previously called 2019-novel coronavirus (2019-nCoV), is currently designated as the severe respiratory syndrome coronavirus-2 (SARS-CoV-2). On January 23, Wuhan was locked down, and the World Health Organization (WHO) declared a “public health emergency of international concern.” The viral genome of SARS-CoV-2 is around 29.8 kilobase, containing six major open reading frames. The most common clinical symptoms were fever, cough, fatigue, shortness of breath, dyspnea, muscle ache, headache, chest pain, vomiting, sore throat, and sputum production. The main mode of transmission is through respiratory particles. The incubation period is 3 to 7 days. Both asymptomatic and symptomatic patients seem to be infectious. Spike (S) proteins of SARS-CoV-2 seem to have a 10- to 20-fold higher affinity to the human angiotensin enzyme 2 (ACE2) receptor than that of SARS-CoV. The high affinity of S protein to theACE2 receptor, and the additional advantages offered by the transfection facilitators Furin and Neutropilin-1, likely, contributes to the rapid spreading of this novel virus. Since these receptors are highly expressed on a variety of cells, including vascular endothelial cells and adipose tissue, individuals with compromised function of these tissues drive greater infection and severity in patients with COVID-19. Global health experts estimate that one in five individuals worldwide could be at risk for severe COVID-19, due to underlying health conditions. There is a great need for a rapid, specific, cost-effective test for monitoring the infected individuals. Even though a 15- minute, antigen test was made available by Abbott recently, it seems that the schools, colleges, and business establishments lack the ability to use these tests effectively to keep their businesses open safely. Management of the infected individuals seems to be based on clinical symptoms that manifest as the disease progresses. The US Food & Drug Administration (FDA), has created a special emergency program for possible therapies, the Coronavirus Treatment Acceleration Program (CTAP). The program uses every available method to move new and emerging treatments as quickly as possible, keeping in mind the safety and efficacy of such therapies. According to the WHO report, there are currently more than 150 COVID-19 vaccine candidates under development. Several vaccines are in Phase 3 clinical trials. In an unprecedented effort, one of the experimental monoclonal antibody cocktails of Regeneron was used for therapeutic purposes when the US president was tested positive for COVID-19. There are no drugs or other therapeutics approved by the US FDA to prevent or treat COVID-19. The National Institutes of Health (NIH) have published interim guidelines for the medical management of COVID-19. In the absence of a cure, the only choice we all have is to follow the best practices recommended by the public health experts—use of face masks (coverings), frequent hand washing with soap, contact tracing of infected individuals, and quarantining COVID-19 positive individuals, till they are free of the highly infectious virus.