Attenuated Salmonella carrying plasmid co-expressing HPV16 L1 and siRNA-E6 for cervical cancer therapy

Human papillomavirus (HPV) infection is the major etiological factor for cervical cancer. HPV prophylactic vaccines based on L1 virus-like particles have been considered as an effective prevention method. However, existing recombination vaccines are too expensive for developing countries. DNA vaccines might be a lower-cost and effective alternative. In this study, a plasmid (pcDNA3.1-HPV16-L1) and a co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) carried by attenuated Salmonella were constructed and their prevention and treatment effect on cervical cancer were observed, respectively. The results showed that pcDNA3.1-HPV16-L1 carried by attenuated Salmonella could induce the production of HPV16-L1 antibodies, IL-2 and INF-γ in mice serum, which presented its prevention effect on HPV. Subsequently, E6 and E7 gene silencing by pCG-siE6 inhibited the growth of cervical cancer both in vitro and in vivo. Furthermore, L1 up-regulation and E6/E7 down-regulation caused by co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) contributed to a significant anti-tumor effect on the mice. This study suggests that pcDNA3.1-HPV16-L1-siE6 carried by attenuated Salmonella has a synergistic effect of immune regulation and RNA interference in cervical cancer treatment.

Application of Nanomaterials as an Advanced Strategy for the Diagnosis, Prevention, and Treatment of Viral Diseases

The coronavirus disease (COVID-19) pandemic poses serious global health concerns with the continued emergence of new variants. The periodic outbreak of novel emerging and re-emerging infectious pathogens has elevated concerns and challenges for the future. To develop mitigation strategies against infectious diseases, nano-based approaches are being increasingly applied in diagnostic systems, prophylactic vaccines, and therapeutics. This review presents the properties of various nanoplatforms and discusses their role in the development of sensors, vectors, delivery agents, intrinsic immunostimulants, and viral inhibitors. Advanced nanomedical applications for infectious diseases have been highlighted. Moreover, physicochemical properties that confer physiological advantages and contribute to the control and inhibition of infectious diseases have been discussed. Safety concerns limit the commercial production and clinical use of these technologies in humans; however, overcoming these limitations may enable the use of nanomaterials to resolve current infection control issues via application of nanomaterials as a platform for the diagnosis, prevention, and treatment of viral diseases.

Review of Influenza Virus Vaccines: The Qualitative Nature of Immune Responses to Infection and Vaccination Is a Critical Consideration

Influenza viruses have affected the world for over a century, causing multiple pandemics. Throughout the years, many prophylactic vaccines have been developed for influenza; however, these viruses are still a global issue and take many lives. In this paper, we review influenza viruses, associated immunological mechanisms, current influenza vaccine platforms, and influenza infection, in the context of immunocompromised populations. This review focuses on the qualitative nature of immune responses against influenza viruses, with an emphasis on trained immunity and an assessment of the characteristics of the host–pathogen that compromise the effectiveness of immunization. We also highlight innovative immunological concepts that are important considerations for the development of the next generation of vaccines against influenza viruses.

Vaccine Design and Vaccination Strategies against Rickettsiae

Rickettsioses are febrile, potentially lethal infectious diseases that are a serious health threat, especially in poor income countries. The causative agents are small obligate intracellular bacteria, rickettsiae. Rickettsial infections are emerging worldwide with increasing incidence and geographic distribution. Nonetheless, these infections are clearly underdiagnosed because methods of diagnosis are still limited and often not available. Another problem is that the bacteria respond to only a few antibiotics, so delayed or wrong antibiotic treatment often leads to a more severe outcome of the disease. In addition to that, the development of antibiotic resistance is a serious threat because alternative antibiotics are missing. For these reasons, prophylactic vaccines against rickettsiae are urgently needed. In the past years, knowledge about protective immunity against rickettsiae and immunogenic determinants has been increasing and provides a basis for vaccine development against these bacterial pathogens. This review provides an overview of experimental vaccination approaches against rickettsial infections and perspectives on vaccination strategies.

Information Opacity in Biopharmaceutical Innovation Through the Lens of COVID-19

The COVID-19 pandemic has revealed myriad and complex challenges for our national health care system spanning preparedness, response, access, costs, infrastructure, coordination, and medical innovation. These challenges implicate federal, state, and local agencies and actors, as well as international collaborative bodies. One constant throughout the pandemic has been the pressing need for safe and effective diagnostics, prophylactic vaccines, and drug treatments to counter the virus.1 Inarguably, significant problems with the multi-faceted system of drug and vaccine innovation and regulation manifested long before the COVID-19 pandemic.2 The pandemic, however, has laid bare the inextricable connections among federal funding, patents, product review and approval mechanisms, and the eventual medical products and resulting costs.

Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines.

An AAV-ie based Vaccine effectively protects against SARS-CoV-2 and Circulating Variants

Prophylactic vaccines against SARS-CoV-2 have been extensively developed globally to overcome the COVID-19 pandemic. However, recently emerging SARS-CoV-2 variants B.1.1.7 and B.1.351 limit the vaccine protection effects and successfully escape antibody cocktail treatment. Herein, based on our previously engineered adeno-associated viral (AAV) vector, AAV-ie, and systematic immunogen screening, we developed an AAV-ie-S1 vaccine with thermostability, high efficiency, safety, and single-dose vaccination advantage. Importantly, the AAV-ie-S1 immune sera efficiently neutralize B.1.1.7 and B.1.351, indicating a potential to circumvent the spreading of SARS-CoV-2.

VERIFICATION OF VIABILITY AND PHENOTYPICAL PROPERTIES OF STRAINS INFECTIOUS AGALACTIC OF SHEEP AND GOATS

The article provides data about the first cases of detection and spread of infectious agalactia in sheep and goats, both in Russia and abroad. It was revealed that these are mainly regions with traditional sheep breeding, which include regions of Europe, Asia, Africa, as well as countries locat-ed along the shores of the Mediterranean Sea. The success of preventing and eradicating this disease depends on the availability of prophylactic vaccines and diagnostic drugs. The basis for their manu-facture is the production and control strains of the pathogen, which are obtained by biological en-terprises of the agro-industrial complex from the state collections of microorganisms. In the collec-tions, strains are studied at the frequency indicated in the passport, and optimal conditions are cre-ated to prevent microorganisms from losing their viability and their biological properties during long-term storage. The present work shows results of studies of strains A-319 and 8899 of the caus-ative agent of infectious agalactia in sheep and goats stored for 20 years, in a lyophilized form. The data obtained for determining the viability and studying the biological properties of the strains showed their compliance with the passport data.