Research Terms
This coronavirus vaccine composition generates sterilizing immunity and prevents active infection of dogs and cats with canine and feline coronaviruses. Coronaviruses (CoVs) are a highly diverse family of enveloped positive-sense, single-stranded RNA viruses with a lipid envelope. They can infect humans and other mammals, including livestock, companion animals, and avian species. In the coronavirus family, recombination is very common, which can result in the generation of new variants capable of infecting outside their natural host species.
Feline (FCoV) and canine (CCoV) coronaviruses are widespread among dog and cat populations. Two feline coronavirus serotypes, serotypes 1 and 2 (FCoV1 and FCoV2), are known, infecting the epithelial cells of the gastrointestinal tract, and causing mild gastrointestinal disease, symptoms including diarrhea, vomiting, and transient weight loss in domestic cats and, especially, kittens. Upon chronic infection, these viruses may mutate into pathogenic and fatal variants, such as feline infectious peritonitis viruses (FIPVs). No successful FIPV treatments are available in US since the drug remdesivir cannot be purchased legally for the treatment of pet cats. Furthermore, antibody-dependent enhancements of FCoV and FIPV infections, whereby the vaccine results in the generation of enhancing antibodies making the infection worse, also hampering vaccine development.
For humans, in the last two decades, three highly pathogenic and deadly human coronaviruses emerged, with SARS-CoV2 (SCoV2), the virus causing the current COVID-19 pandemic, among them. SCoV2 originated from recombination events between coronaviruses of other species, one or more intermediate hosts. While vaccines have partially controlled the COVID-19 pandemic, their efficacy wanes over time, necessitating booster doses. In addition, vaccinations have not prevented “breakthrough” infections or the emergence and rapid spread of “variants of concern,” such as the Delta and Omicron variants. There is evidence of SARS-CoV-2 spillover from humans to animals, with infections reported in dogs, cats, tigers, lions, gorillas, and minks. Infected cats display mild-to-moderate respiratory symptoms, and dogs develop no or mild respiratory symptoms. An inevitable event of a cat-to-human transmission of Delta variant was reported in July 2022. A vaccine that is protective across multiple species, that protects vaccinated animals from infection and disease symptoms, and reduces opportunities for new zoonotic variants to arise with the potential for human reinfection, is a critical component to protect against the next coronavirus pandemic.
Researchers at the University of Florida have developed a pan-coronavirus (CoV) vaccine for dogs and cats, providing protection against infection by feline (FCoV) and canine (CCoV) coronaviruses, respectively. The vaccine composition generates sterilizing immunity against multiple coronavirus serotypes. This same approach can potentially yield the development of vaccines for humans with durable immunity against multiple SCoV2 variants.
A pan-coronavirus (CoV) vaccine formulation for dogs and cats generates sterilizing immunity and prevents infection by feline and canine coronaviruses
This coronavirus (CoV) vaccine is protective across multiple species, generating sterilizing immunity against infection by canine (CCoV) and feline (FCoV) coronaviruses. The formulation comprises a feline coronavirus (FCoV) receptor-binding domain (RBD) peptide and a severe acute respiratory syndrome coronavirus 2 (SCoV2) RBD peptide. The sera from feline coronaviruses (FCoVs) infected cats cross-react strongly with SARS-CoV2 (SCoV2) RBD, and both feline coronavirus serotype 2 (FCoV2) RBD and SCoV2 RBD can block the in vitro FCoV2 infection of feline cells. This discovery makes the University of Florida researchers the first to determine the functional sequence of FCoV2 RBD. The ability of FCoV2 and SCoV2 RBDs to block FCoV2 infection suggests an FCoV2 vaccine can be generated using FCoV2 RBD alone or in combination with SCoV2 RBD.
Furthermore, the researchers determined the canine coronavirus serotype 2 (CCoV2) and FCoV RBDs to have a 95.9% amino acid sequence similarity and 88.1% amino acid sequence identity. Feline coronavirus serotype 1 (FCoV1) and canine coronavirus serotype 1 (CCoV1) RBDs have an amino acid sequence similarity of 81.4%, indicating a common lineage. These findings make the potential development of a pan-coronavirus vaccine possible. The vaccine composition stimulates a potent and safe immune response in cats and dogs, preventing active infection by FCoV and CCoV. In preventing active infections, the vaccine also indirectly inhibits the development of new highly pathogenic and deadly coronavirus variants with the potential to infect humans.
This cancer vaccine stimulates the production of antibodies against a cell surface antigen common to both melanoma and osteosarcoma tumors and works in conjunction with chemotherapy. Melanoma is an aggressive form of skin cancer that’s highly metastatic at later stages. Osteosarcoma is the most common form of bone cancer and also is highly metastatic. Beyond chemotherapy, which is only moderately effective and has numerous side effects, physicians may employ immunotherapies such as adoptive T-cell therapies to treat these and other cancers. Because T-cell therapies involve delivering live whole cells, administration must wait until after chemotherapy. Since cancers are typically able to evade destruction by the immune system, cancer vaccines aim to encourage the immune system to attack cancer cells by eliciting an immune response against tumor-specific antigens. However, developing effective cancer vaccines has proven challenging due to the difficulty of eliciting a robust and consistent immune response against "self" antigens. The global market for cancer vaccines is estimated to have over a 12% growth rate, reaching almost $12 billion by 2026.
Researchers at the University of Florida have developed a vaccine for melanoma and osteosarcoma cancers based on the tumor-specific antigen disialoganglioside (GD3). The nano-liposome composition of the vaccine enhances its stability and stimulates a robust response by both the innate and adaptive arms of the immune system, even during the administration of chemotherapy.
Cancer vaccine that targets GD3 antigen to treat melanoma and osteosarcoma
This nanolipo-GD3 vaccine enhances the production of antibodies that target tumor cells expressing the disialoganglioside (GD3) antigen. Both melanoma and osteosarcoma tumor cells express the antigen, thus potentially resulting in a single vaccine that effectively targets both of these common and hard to treat cancers. This cancer vaccine is an “off the shelf” immunotherapy, that is effective without requiring customization for each patient. The vaccine is able to stimulate an immune response even during a chemotherapy treatment regimen. UF’s scientists have demonstrated in dogs with melanoma that the vaccine improved survival by two- to three-fold with a course of four intradermal injections of the vaccine. Humans and dogs with melanoma have shared histopathologic and genetic features, especially in the oral mucosal forms, making dogs an ideal large animal translational model for this study. In the case of osteosarcoma, when the vaccine is given with standard of care the median survival is 552 days compared to 292-310 days for standard of care alone.