Developing a Live Probiotic Vaccine Based on the Enterococcus faecium L3 Strain Expressing Influenza Neuraminidase

Probiotic microorganisms are currently considered as a promising platform for the development of recombinant vaccines expressing foreign antigens. In this study, we generated and evaluated the live mucosal recombinant vaccine by integrating genes encoding influenza virus neuraminidase (NA) of the N2 subtype into the DNA of the probiotic strain Enterococcus faecium L3 (L3). We confirmed NA expression in the pili of L3 using immune electron microscopy. Mice were fed with a probiotic vaccine containing the NA gene (L3-NA) or pure L3. Oral administration of L3-NA caused detectable increase in virus-specific serum IgG and local IgA after the third feeding. Immunization with L3-NA increased the survival rate by 34% when the mice were infected using A(H1N1)pdm09 influenza virus after the third feeding. After S. pneumoniae post-influenza infection, the L3-NA-immunized mice were 50% more protected from lethality in comparison with L3-fed mice. Thus, a live probiotic vaccine candidate based on L3 induced the formation of systemic and local immunity and provide partial protection against complicated influenza.

Recent Development of Ruminant Vaccine Against Viral Diseases

Pathogens of viral origin produce a large variety of infectious diseases in livestock. It is essential to establish the best practices in animal care and an efficient way to stop and prevent infectious diseases that impact animal husbandry. So far, the greatest way to combat the disease is to adopt a vaccine policy. In the fight against infectious diseases, vaccines are very popular. Vaccination's fundamental concept is to utilize particular antigens, either endogenous or exogenous to induce immunity against the antigens or cells. In light of how past emerging and reemerging infectious diseases and pandemics were handled, examining the vaccination methods and technological platforms utilized for the animals may provide some useful insights. New vaccine manufacturing methods have evolved because of developments in technology and medicine and our broad knowledge of immunology, molecular biology, microbiology, and biochemistry, among other basic science disciplines. Genetic engineering, proteomics, and other advanced technologies have aided in implementing novel vaccine theories, resulting in the discovery of new ruminant vaccines and the improvement of existing ones. Subunit vaccines, recombinant vaccines, DNA vaccines, and vectored vaccines are increasingly gaining scientific and public attention as the next generation of vaccines and are being seen as viable replacements to conventional vaccines. The current review looks at the effects and implications of recent ruminant vaccine advances in terms of evolving microbiology, immunology, and molecular biology.

Modern technologies for the production of vaccines against avian infectious diseases

Vaccination is one of the most effective and versatile ways to prevent infectious diseases. The development of modern technologies makes it possible to obtain vaccines with desired properties. The review presents data on different types of vaccines used for the prevention of infectious diseases of birds. The advantages and disadvantages of traditional attenuated and inactivated vaccines, as well as recombinant vaccines vector, subunit, based on virus-like particles and DNA vaccines are considered. Possibilities of bacterial, yeast, baculovirus and plant systems for the expression of heterologous genes for the production of recombinant vaccines are discussed.

Genetic Diversity of Microneme Protein 2 and Surface Antigen 1 of Eimeria tenella

Avian coccidiosis is a disease caused by members of the genus Eimeria. Huge economic losses incurred by the global poultry industry due to coccidiosis have increased the need for cost-effective and easily available recombinant vaccines. Microneme protein 2 (MIC2) and surface antigen 1 (SAG1) of E. tenella have been recognised as potential vaccine candidates. However, the genetic diversity of the antigens in field isolates, which affects vaccine efficacy, has yet to be largely investigated. Here, we analysed genetic diversity and natural selection of etmic2 and etsag1 in Korean E. tenella isolates. Both genes exhibited low levels of genetic diversity in Korean isolates. However, the two genes showed different patterns of nucleotide diversity and amino acid polymorphism involving the E. tenella isolates obtained from different countries including China and India. These results underscore the need to investigate the genetic diversity of the vaccine candidate antigens and warrant monitoring of genetic heterogeneity and evolutionary aspects of the genes in larger numbers of E. tenella field isolates from different geographical areas to design effective coccidial vaccines.

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10–15% of infected individuals and mortality in 2–3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the “cold chain” transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS-CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.

Development of live vaccine based on the Enterococcus faecium L3 vector for prevention influenza infections

Probiotic microorganisms are currently considered as a promising platform for the development of recombinant vaccines expressing foreign antigens. In this study we generated and evaluated the live mucosal recombinant vaccine by integrating genes encoding influenza virus neuraminidase (NA) of N2 subtype into the DNA of the probiotic strain Enterococcus faecium L3 (L3). We confirmed NA expression in the pili of L3 using immune electron microscopy. Mice were fed with a probiotic vaccine containing the NA gene (L3-NA) or pure L3. Oral administration of L3-NA caused detectable increase of virus-specific serum IgG and local IgA after the third feeding. A the same time, single spleen cell suspensions were stimulated with whole A(H1N1)pdm09 virus followed by flow cytometry. In mice received L3-NA, the content of cytotoxic T-lymphocytes was more pronounced compared to mice receiving pure L3. Immunization with L3-NA increased the survival rate by 34% when the mice were infected using A(H1N1)pdm09 influenza virus after the third feeding. After S. pneumonia post-influenza infection, the L3-NA immunized mice were 50% more protected from lethality in comparison with L3 fed mice. Thus, a live probiotic vaccine candidate based on L3 induced the formation of systemic and local immunity and provide protection against complicated influenza. The approach based on a probiotic vaccine expressing viral epitopes can allow repeated immunization during epidemic season.

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the cold chain transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS-CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.