Vaccines for Virus from Coronaviridae Family

Creative Biolabs is a world leader in the field of viral vaccine development. With our strong expertise and advanced platform in vaccine field, we are therefore confident in offering the best vaccine development services for different types of diseases caused by virus from coronaviridae family, including coronaviruses and canine coronavirus, bovine coronavirus, SARS, and MERS coronavirus. We guarantee the finest results for our customers all over the world.

Coronaviridae is a family of single-stranded, enveloped, positive RNA viruses. Coronaviridae family is comprised of two genera which are coronavirus and torovirus. Coronaviruses are well-established pathogens of humans, mammals, and birds while the toroviruses are recognized as causes of animal diarrhoea. Both are capable of causing a mild respiratory and enteric infection in humans and other vertebrate animals. Vaccines targeting several coronaviruses have been developed, and some have been demonstrated to be efficacious in preventing viral infection. Coronaviruses are also known to cause severe infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).

Introduction of Coronaviruses

Structure of coronavirus.

Coronaviruses (CoVs) are characterized by club-shaped spike projections emanating from their surface of the virion, an unusually large RNA genome, and a unique replication strategy. The structure of CoVs comprises the spike (S), envelope (E), membrane (M), and nucleocapsid (N). The CoVs replication occurs in the enterocytes of the small intestine and is limited to the upper two-thirds of the small intestine and local lymph nodes. Infection starts with receptor binding via the S protein and entry by membrane fusion. Before entry to the cells, the virus particle is uncoated and the RNA genome is deposited into the cytoplasm. After uncoating, the genomic RNA is used as a template to synthesize progeny genomes and a nested set of subgenomic RNAs. The replication transcription centers are closely associated with double membrane vesicles (DMVs), which are proposed to be adopted from the modified endoplasmic reticulum (ER), possibly by the combined activities of non-structural proteins nsp3, nsp4, and nsp6. The S, E, and M proteins are synthesized and anchored on the ER, whereas the N protein is translated in the cytosol. Assembly takes place in the ER-Golgi intermediate compartment (ERGIC) and mature virions are released via smooth-walled vesicles by exocytosis. There have three stages that induce ER stress namely: (1) formation of DMVs, (2) massive production and modification of structural proteins, and (3) depletion of ER membrane during budding.

Schematic diagram showing the replication cycle of coronavirus.

Fig 2. Schematic diagram showing the replication cycle of coronavirus.

Canine Coronavirus Vaccines

Canine coronavirus (CCoV) causes contagious enteritis of variable severity in the dog population. Although dogs of all ages appear to be susceptible to infection by CCoV, the condition is probably most important as an uncommon, transient, generally nonfatal diarrhea in puppies. The disease is caused by CCoV which could spread from dog to dog through contact with feces. Two types of vaccines against canine coronavirus are available, which can be inactivated coronavirus, or combination vaccines with others which can offer the broad protection for dogs.

Bovine Coronavirus Vaccines

Bovine coronavirus (BoCV) is a major cause of diarrhea in young calves and winter dysentery in dairy cows, and the same strains occasionally induce respiratory disease in calves 2-16 weeks of age. The virus can infect both domestic and wild ruminants and has a worldwide distribution. The way of transmission is horizontal, via oro-fecal or respiratory routes.

We are developing several vaccines which are recommended for use in healthy calves as an aid in the reduction of enteric disease caused by BoCV. The vaccines can help the cattle’s immune system produce more BCoV antibodies to fight the disease and protect the herd from catching virus through other infected cattle. Animals should be treated symptomatically. The disease can be controlled by vaccinating the dam with a live vaccine, a modified live virus and a monovalent MLV vaccine prepared with a respiratory BCoV strain. Besides vaccination and adequate colostrum intake in newborn calves, using appropriate hygiene methods and ventilation of housing can reduce disease incidence.

SARS Vaccines

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease caused by SARS-associated coronavirus (SARS-CoV). Originated in the Guangdong province of China in late 2002, SARS seriously threatened public health and socioeconomic stability worldwide. An ideal SARS vaccine should have three features as follows: 1) elicit highly potent neutralizing antibody responses against a broad spectrum of viral strains; 2) induce protection against infection and transmission; and 3) be safe by not inducing any infection-enhancing antibodies or harmful immune or inflammatory responses.

Several SARS vaccines are available, including inactivated SARS-CoV-based vaccines, S protein-based vaccines, and vaccines based on fragments containing neutralizing epitopes. Recombinant vector-based vaccines can induce potent neutralizing and protective responses in immunized animals but may induce antibodies that enhance infection by early human SARS-CoV and animal SARS-CoV-like viruses. Recombinant RBD (receptor-binding domain) consists of multiple conformational neutralizing epitopes that induce highly potent neutralizing antibodies against SARS-CoV. RBD does not contain immunodominant sites that induce nonneutralizing antibodies. RBD sequences are relatively conserved.

Middle East Respiratory Syndrome (MERS) Vaccine

Middle East Respiratory Syndrome (MERS) is a viral respiratory illness that is new to humans, especially the elderly and people with comorbidities. The virus that causes MERS is called MERS Coronavirus (MERS-CoV). Coronavirus is a common virus that most people infected in their life. Human coronaviruses usually cause mild to moderate cold-like illnesses.

Efforts to prevent MERS by immunization are based in part on the extensive information gained from studies of coronavirus vaccines used to prevent infections in domesticated and companion animals. Recombinant adenoviruses, poxviruses, and measles virus expressing full-length S protein or the extracellular S1 domain have been engineered and tested in experimentally infected animals. All were able to induce an anti-S protein antibody response. Live attenuated MERS-CoV vaccines would be an excellent vaccine candidate. DNA vaccines that induce MERS-CoV-specific antibody and T-cell responses have been shown to be efficacious in non-human primates. Vaccines expressing the MERS-CoV receptor binding domain (RBD) induced potent neutralizing antibodies in mice and neutralizing antibodies and T-cell responses in non-human primates.

Creative Biolabs can offer high-quality customized services by adjusting protocols to meet even the most specific requirements. We are pleased to share our cutting-edge technology and extensive expertise in the field of viral vaccine development. If you are interested in our services, please contact us for more details.

Reference

  1. To S. Fung. (2014). “Coronavirus infection, ER stress, apoptosis and innate immunity.” Front. Microbiol. 5, 1-8.

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