Coronavirus Vaccine Development Research Articles

Insights into structural vaccinology harnessed for universal coronavirus vaccine development.

Structural vaccinology is pivotal in expediting vaccine design through high-throughput screening of immunogenic antigens. Leveraging the structural and functional characteristics of antigens and immune cell receptors, this approach employs protein structural comparison to identify conserved patterns in key pathogenic components. Molecular modeling techniques, including homology modeling and molecular docking, analyze specific three-dimensional (3D) structures and protein interactions and offer valuable insights into the 3D interactions and binding affinity between vaccine candidates and target proteins. In this review, we delve into the utilization of various immunoinformatics and molecular modeling tools to streamline the development of broad-protective vaccines against coronavirus disease 2019 variants. Structural vaccinology significantly enhances our understanding of molecular interactions between hosts and pathogens. By accelerating the pace of developing effective and targeted vaccines, particularly against the rapidly mutating severe acute respiratory syndrome coronavirus 2 and other prevalent infectious diseases, this approach stands at the forefront of advancing immunization strategies. The combination of computational techniques and structural insights not only facilitates the identification of potential vaccine candidates but also contributes to the rational design of vaccines, fostering a more efficient and targeted approach to combatting infectious diseases.

Towards a Safer Future: Enhancing Vaccine Development to Combat Animal Coronaviruses.

Coronaviruses (CoVs) are a large class of positively stranded RNA viruses that pose a significant threat to public health, livestock farming, and wild animals. These viruses have the ability to cross species barriers and cause devastating epidemics. Animals are considered to be intermediate hosts for many coronaviruses, and many animal coronaviruses also have the potential for cross-species transmission to humans. Therefore, controlling the epidemic transmission of animal coronaviruses is of great importance to human health. Vaccination programs have proven to be effective in controlling coronaviruses infections, offering a cost-effective approach to reducing morbidity and mortality, so the re-emergence of lethal coronaviruses emphasizes the urgent need for the development of effective vaccines. In this regard, we explore the progress in animal coronavirus vaccine development, covering the latest taxonomy of the main animal coronaviruses, spillover events, diverse vaccine development platforms, potential main targets for animal coronavirus vaccine development, and primary challenges facing animal coronavirus vaccines. We emphasize the urgent need to create a "dual-effect" vaccine capable of eliciting both cellular and humoral immune responses. The goal is to highlight the contributions of veterinary scientists in this field and emphasize the importance of interdisciplinary collaboration between the veterinary and medical communities. By promoting communication and cooperation, we can enhance the development of novel and super vaccines to combat human and animal coronavirus infections in the future.

Targeting the conserved coronavirus octamer motif GGAAGAGC is a strategy for the development of coronavirus vaccine

BackgroundCoronaviruses are pathogens of humans and animals that cause widespread and costly diseases. The development of effective strategies to combat the threat of coronaviruses is therefore a top priority. The conserved coronavirus octamer motif 5’GGAAGAGC3’ exists in the 3’ untranslated region of all identified coronaviruses. In the current study, we aimed to examine whether targeting the coronavirus octamer motif GGAAGAGC is a promising approach to develop coronavirus vaccine.MethodsPlaque assays were used to determine the titers of mouse hepatitis virus (MHV)-A59 octamer mutant (MHVoctm) and wild-type (wt) MHV-A59 (MHVwt). Western blotting was used for the determination of translation efficiency of MHVoctm and MHVwt. Plaque assays and RT-qPCR were employed to examine whether MHVoctm was more sensitive to interferon treatment than MHVwt. Weight loss, clinical signs, survival rate, viral RNA detection and histopathological examination were used to evaluate whether MHVoctm was a vaccine candidate against MHVwt infection in BALB/c mice.ResultsIn this study, we showed that (i) the MHVoctm with mutation of coronavirus octamer was able to grow to high titers but attenuated in mice, (ii) with the reduced multiplicity of infection (MOI), the difference in gene expression between MHVoctm and MHVwt became more evident in cultured cells, (iii) MHVoctm was more sensitive to interferon treatment than MHVwt and (iv) mice inoculated with MHVoctm were protected from MHVwt infection.ConclusionsBased on the results obtained from cultured cells, it was suggested that the synergistic effects of octamer mutation, multiplicity of infection and immune response may be a mechanism explaining the distinct phenotypes of octamer-mutated coronavirus in cell culture and mice. In addition, targeting the conserved coronavirus octamer motif is a strategy for development of coronavirus vaccine. Since the conserved octamer exists in all coronaviruses, this strategy of targeting the conserved octamer motif can also be applied to other human and animal coronaviruses for the development of coronavirus vaccines, especially the emergence of novel coronaviruses such as SARS-CoV-2, saving time and cost for vaccine development and disease control.

Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) marks the third novel β-coronavirus to cause significant human mortality in the last two decades. Although vaccines are available, too few have been administered worldwide to keep the virus in check and to prevent mutations leading to immune escape. To determine if antibodies could be identified with universal coronavirus activity, plasma from convalescent subjects was screened for IgG against a stabilized pre-fusion SARS-CoV-2 spike S2 domain, which is highly conserved between human β-coronavirus. From these subjects, several S2-specific human monoclonal antibodies (hmAbs) were developed that neutralized SARS-CoV-2 with recognition of all variants of concern (VoC) tested (Beta, Gamma, Delta, Epsilon, and Omicron). The hmAb 1249A8 emerged as the most potent and broad hmAb, able to recognize all human β-coronavirus and neutralize SARS-CoV and MERS-CoV. 1249A8 demonstrated significant prophylactic activity in K18 hACE2 mice infected with SARS-CoV-2 lineage A and lineage B Beta, and Omicron VoC. 1249A8 delivered as a single 4 mg/kg intranasal (i.n.) dose to hamsters 12 hours following infection with SARS-CoV-2 Delta protected them from weight loss, with therapeutic activity further enhanced when combined with 1213H7, an S1-specific neutralizing hmAb. As little as 2 mg/kg of 1249A8 i.n. dose 12 hours following infection with SARS-CoV Urbani strain, protected hamsters from weight loss and significantly reduced upper and lower respiratory viral burden. These results indicate in vivo cooperativity between S1 and S2 specific neutralizing hmAbs and that potent universal coronavirus neutralizing mAbs with therapeutic potential can be induced in humans and can guide universal coronavirus vaccine development.

Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species.

Although COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging on development of multispecies coronavirus vaccines. Here we develop prototype lipid nanoparticle (LNP)-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV, and MERS-CoV, and we test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and duplex LNP-mRNA vaccinations induce antigen-specific antibody responses against SARS-CoV-2, SARS-CoV, and MERS-CoV. Single-cell RNA sequencing profiles the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing a systemic increase in activated B cells and differential gene expression across major adaptive immune cells. Sequential vaccination shows potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrate the feasibility, antibody responses, and single-cell immune profiles of multispecies coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights into optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.

Broadly neutralizing antibodies target the coronavirus fusion peptide.

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We use an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.

Acceptance of COVID-19 Vaccine and Its Associated Factors Among Ethiopian Population: A Systematic Review.

IntroductionCoronavirus disease 2019 (COVID-19) is a global health threat. Millions of lives were lost to COVID-19 and it has caused a substantial economic crisis throughout the world. The development of coronavirus vaccines has pinned a new hope in combating the pandemic. The success of vaccination and development of herd immunity highly depend on the willingness to be vaccinated, not merely on the availability of a vaccine. This review aims to provide comprehensive evidence on acceptance of COVID-19 vaccine and its associated factors in Ethiopia.MethodsLiterature searching was done using PubMed, Google scholar and Science direct databases. Studies conducted in Ethiopia, published in English language from inception until January 9, 2022 were included. Retrieved articles were screened based on titles, abstracts and full text reading to identify studies that met the inclusion criteria. About 21 eligible studies were included in this systematic review. The data were extracted using a data extraction checklist.ResultsA total of 2058 records were retrieved, of which 21 were eligible for this systematic review. All of the articles were cross-sectional studies published in 2021. In Ethiopia, the level of COVID-19 vaccine acceptance ranged from 31.4% to 92.33%. The vaccine acceptance level was significantly associated with age groups, sex, educational status, perceived susceptibility, perceived benefit, knowledge about COVID-19 vaccine, and other socio-demographic factors.ConclusionA significant portion of the studies revealed vaccine acceptance level was low. Variation of vaccine acceptance was associated with socio-demographic factors (age, sex, educational status, etc.), information-related factors, and other health-related behaviors. Dissemination of clear and adequate information concerning the vaccine might be the required prior activity to increase acceptance of the vaccine. Hence, there should be a coordinated effort to halt the pandemic through increasing the acceptance of COVID−19 vaccine.

Human challenge studies in the time of COVID-19: Pros and cons

Can we speed up coronavirus vaccine development? A human challenge study, in which volunteers would be deliberately infected with coronavirus, could help in theory. In this article, two collaborators from the CTU Geneva explore the potential benefits and the risks associated with SARS-CoV-2 challenge studies.

Patient organisations: COVID-19 concerns related to human research

Patient organisations support and advocate for the patient communities they represent while also increasing the role of patients in improving and shaping healthcare practices, policies, and systems. During the coronavirus pandemic, patient organisations have provided their patient communities with relevant information on COVID-19 and have brought patients’ perspectives into the dialogue around COVID-19. Moreover, they have advocated for patients’ needs and concerns related to the pandemic’s effects on human research and to coronavirus vaccine development and authorisation. This article summarises several of the issues facing patient communities during the pandemic and provides examples of patient organisations’ responses to these issues.

Piglet immunization with a spike subunit vaccine enhances disease by porcine epidemic diarrhea virus

Immunization with an insect cell lysate/baculovirus mixture containing recombinant porcine epidemic diarrhea virus (PEDV) spike protein induced high levels of neutralizing antibodies in both mice and piglets. However, immunization of piglets with this vaccine resulted in enhancement of disease symptoms and virus replication in vaccine recipients exposed to PEDV challenge. Thus, these observations demonstrate a previously unrecognized challenge of PEDV vaccine research, which has important implications for coronavirus vaccine development.

Recent advances in vaccine development of severe acute respiratory syndrome coronavirus 2

[Abstract] The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic. The pathogen responsible for this disease is a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It belongs to coronavirus family, a pathogen similar to SARS and Middle East respiratory syndrome (MERS), and manifests strong infectivity and pathogenicity to progress into severe pneumonia. Till now, there is no specific therapeutic drug targeting against this virus. With the rapid spread and deterioration of the epidemic situation, vaccination has become an urgent need. This review introduces the immune defense mechanism of human body against coronavirus briefly, set forth the key viral spike protein for coronavirus vaccine development, and then summarize the recent advances/progresses and potential challenges in safety and efficacy of vaccine development for SARS-CoV-2.

Adjuvants for Coronavirus Vaccines.

Vaccine development utilizing various platforms is one of the strategies that has been proposed to address the coronavirus disease 2019 (COVID-19) pandemic. Adjuvants are critical components of both subunit and certain inactivated vaccines because they induce specific immune responses that are more robust and long-lasting. A review of the history of coronavirus vaccine development demonstrates that only a few adjuvants, including aluminum salts, emulsions, and TLR agonists, have been formulated for the severe acute respiratory syndrome-associated coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and currently the SARS-CoV-2 vaccines in experimental and pre-clinical studies. However, there is still a lack of evidence regarding the effects of the adjuvants tested in coronavirus vaccines. This paper presents an overview of adjuvants that have been formulated in reported coronavirus vaccine studies, which should assist with the design and selection of adjuvants with optimal efficacy and safety profiles for COVID-19 vaccines.

Research progress and challenges to coronavirus vaccine development

Coronaviruses (CoVs) are nonsegmented, single-stranded, positive-sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.

Induction of the Antiviral Immune Response and Its Circumvention by Coronaviruses.

Some coronaviruses are zoonotic viruses of human and veterinary medical importance. The novel coronavirus, severe acute respiratory symptoms coronavirus 2 (SARS-CoV-2), associated with the current global pandemic, is characterized by pneumonia, lymphopenia, and a cytokine storm in humans that has caused catastrophic impacts on public health worldwide. Coronaviruses are known for their ability to evade innate immune surveillance exerted by the host during the early phase of infection. It is important to comprehensively investigate the interaction between highly pathogenic coronaviruses and their hosts. In this review, we summarize the existing knowledge about coronaviruses with a focus on antiviral immune responses in the respiratory and intestinal tracts to infection with severe coronaviruses that have caused epidemic diseases in humans and domestic animals. We emphasize, in particular, the strategies used by these coronaviruses to circumvent host immune surveillance, mainly including the hijack of antigen-presenting cells, shielding RNA intermediates in replication organelles, 2′-O-methylation modification for the evasion of RNA sensors, and blocking of interferon signaling cascades. We also provide information about the potential development of coronavirus vaccines and antiviral drugs.

Protective Immunity against SARS Subunit Vaccine Candidates Based on Spike Protein: Lessons for Coronavirus Vaccine Development.

The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future.

SARS-CoV-2 spike protein, elaborated

Coronavirus Vaccine development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the trimeric spike protein that initiates infection. Each protomer in the trimeric spike has 22 glycosylation sites. How these sites are glycosylated may affect which cells the virus can infect and could shield some epitopes from antibody neutralization. Watanabe et al. expressed and purified recombinant glycosylated spike trimers, proteolysed them to yield glycopeptides containing a single glycan, and determined the composition of the glycan sites by mass spectrometry. The analysis provides a benchmark that can be used to measure antigen quality as vaccines and antibody tests are developed. Science this issue p. [330][1] [1]: /lookup/doi/10.1126/science.abb9983

WINNING THE COVID WAR AS RESPONSIVE MALAYSIAN CITIZEN: SOCIAL CONFORMITY, SOCIAL COMPLIANCE AND SOCIAL OBEDIENCE

Covid-19 (also known as Coronavirus) was detected initially at Wuhan, China has spread to over 200 countries across the globe. This deadly virus is a threat to mankind as it has killed more than 300,000 and infected more than 5 million people globally. Declared as a pandemic by the World Health Organisation (WHO), momentum is accelerating to speed the development of coronavirus vaccines. Research indicated that this virus is airborne; a person on close contact may get infected from the droplets produced from the infected person during sneezing or coughing. As the virus is given medical attention to cure the infection, equal attention is given to the social aspect to break the chain of COVID. Prevention measures become crucial where many countries have taken unprecedented measures to stop the spreading of the virus by implementing lockdown and social distancing. Lockdown and social distancing are out of norm social conducts, thus adapting them instantaneously and adhering to them at all times are indeed incredible. This study explores social conformity, social compliance and social obedience of responsive citizen in Malaysian context to win the war against COVID.

A pandemic of bad science

ABSTRACT What can epidemiological models tell us about our potential exposure to COVID-19? What progress is being made with regard to coronavirus vaccine development? These days, the general public is asking these questions and more as the COVID-19 pandemic rages on. That there is an extraordinary level of interest in coronavirus news should come as no surprise, but this elevated interest society now has in pandemic-related science has unintended consequences that shouldn’t be ignored. Studies are being rushed to publication even in well-regarded journals. Unvetted articles on so-called preprint servers have received enormous attention. Predatory journals are giving anyone with the ability to pay the opportunity to publish pseudoscience that can be amplified by mainstream news sources. Marketers are exploiting the public’s desperation for protection against COVID-19 and adding a scientific sheen to dubious products. And perhaps-well-meaning experts in data science are producing a raft of arguably meaningless research, creating a distraction at best and wasting valuable resources at worst.

Covid-19 A New Global Outbreak: Diagnosis, Treatment and Prevention

The novel coronavirus (COVID-19) is a pandemic of the new millennium. It was first reported in the Wuhan city, a huge metropolis of 11 million people in central China. The World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic. The virus became named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2), which was nomenclature by the International Committee on Taxonomy of Viruses. Coronavirus is polymorphic spherical particles with spike like surface projections. The envelope of coronavirus consists of a lipid bilayer, where the four membrane protein is anchored i.e. S – spike, E – envelope, M – membrane, N – nucleocapsid. Inside envelop the N protein bound to the positive sense single stranded RNA (+ssRNA) genome. The size of the ssRNA genome is 30000 nucleotide long. The coronavirus probably originated in bats, although it was not clear that how it was transmitted from bats to humans. In keeping with current evidence, coronavirus is transmitted between people through respiratory droplets and close contacts. RT-PCR is the most unique and sensitive for the detection of coronavirus and it is more beneficial for detecting the virus in the primary phase of the infection. It has been observed that there is no vaccine available for the treatment of coronavirus till now, but the S protein is presently considered to be one of the maximum promising targets for coronavirus vaccine development. Here, we review that the biology of the coronavirus in the term of an epidemiology, multiplication, diagnosis, transmission, prevention, treatment.

From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development

The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.