Vaccinia Virus Vectors Research Articles

COVID-19 vaccines: current and future challenges

As of December 2020, around 200 vaccine candidates for Coronavirus Disease 2019 (COVID-19) are being developed. COVID-19 vaccines have been created on a number of platforms and are still being developed. Nucleic acid (DNA, RNA) vaccines, viral vector vaccines, inactivated vaccines, protein subunit vaccines, and live attenuated vaccines are among the COVID-19 vaccine modalities. At this time, at least 52 candidate vaccines are being studied. Spike protein is the primary protein that COVID-19 vaccines are targeting. Therefore, it is critical to determine whether immunizations provide complete or fractional protection, whether this varies with age, whether vaccinated people are protected from reoccurring diseases, and whether they need booster shots if they’ve already been inoculated. Despite the enormous achievement of bringing several vaccine candidates to market in less than a year, acquiring herd immunity at the national level and much more so at the global level remains a major challenge. Therefore, we gathered information on the mechanism of action of presently available COVID-19 vaccines in this review and essential data on the vaccines’ advantages and downsides and their future possibilities.

Development of Long-Term Stability of Enveloped rVSV Viral Vector Expressing SARS-CoV-2 Antigen Using a DOE-Guided Approach

Liquid formulations have been successfully used in many viral vector vaccines including influenza (Flu), hepatitis B, polio (IPV), Ebola, and COVID-19 vaccines. The main advantage of liquid formulations over lyophilized formulations is that they are cost-effective, as well as easier to manufacture and distribute. However, studies have shown that the liquid formulations of enveloped viral vector vaccines are not stable over extended periods of time. In this study, we explored the development of the liquid formulations of an enveloped recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. To do so, we used a design of experiments (DOE) method, which allowed us to assess the stability dynamics of the viral vector in an effective manner. An initial stability study showed that trehalose, gelatin, and histidine were effective at maintaining functional viral titers during freeze–thaw stress and at different temperatures (−20, 4, 20, and 37 °C). These preliminary data helped to identify critical factors for the subsequent implementation of the DOE method that incorporated a stress condition at 37 °C. We used the DOE results to identify the optimal liquid formulations under the selected accelerated stress conditions, which then guided the identification of long-term storage conditions for further evaluation. In the long-term stability study, we identified several liquid formulations made of sugar (sucrose, trehalose, and sorbitol), gelatin, and a histidine buffer that resulted in the improved stability of rVSV-SARS-CoV-2 at 4 °C for six months. This study highlights an effective approach for the development of liquid formulations for viral vector vaccines, contributing significantly to the existing knowledge on enveloped viral vector thermostability.

Evaluation of Tissue Tropism and Horizontal Transmission of a Duck Enteritis Virus Vectored Vaccine in One-Day-Old Chicken

Herpesvirus of turkey (HVT) recombinant vector vaccines are widely used in the poultry industry. However, due to limitations in loading multiple foreign antigens into a single HVT vector, other viral vectors are urgently needed. Since chickens lack maternal immunity to duck enteritis virus (DEV), vector vaccines using DEV as a backbone are currently under study. Even though a recently developed DEV vector vaccine expressing the influenza hemagglutinin H5 of highly pathogenic avian influenza (DEV-H5) induces highly detectable anti-HA antibodies, safety issues hamper further vaccine development. In this work, tissue affinity and horizontal transmission in 1-day-old chickens were systematically evaluated after DEV-H5 vector vaccine inoculation. Sixty percent of DEV-H5-inoculated chickens died between day 2 and day 7 post-inoculation. The displayed clinical signs consisted of lethargy, anorexia, and diarrhea, and virus was shed in feces. Gross and/or histological lesions were recorded in the kidney, heart, intestine, liver, lung, and spleen. Moreover, DEV-H5 replication in intestinal cells caused an increment in interferon-α expression, while occluding junction proteins and ZO-1 expression were significantly upregulated. As a control, birds inoculated with a commercial recombinant turkey herpesvirus expressing the VP2 protein of the infectious bursal disease virus (HVT-VP2) vector vaccine showed neither clinical signs nor mortality. Overall, while the HVT-VP2 vaccine demonstrated complete safety in 1-day-old chickens, our potential DEV-H5 vaccine requires further attenuation for consideration as a vector vaccine candidate in chickens.

Mechanisms and Clinical Applications of Virus-Based Cancer Vaccines

Over the past several decades, immunotherapy as a novel cancer treatment has made tremendous progress. Several categories of immunotherapy have emerged, all designed to stimulate the patients immune system to fight cancer. Cancer vaccines, specifically virus-based cancer vaccines, is a subcategory of immunotherapy that can trigger both innate and adaptive immune response by targeting tumor-specific and tumor-associated antigens. This review summarizes the mechanisms of different types of virus-based cancer vaccines, including inactivated/live attenuated/subunit vaccines, oncolytic virus vaccines, and viral vector vaccines. Furthermore, this review introduces the clinical applications of virus-based cancer vaccines, including oncolytic virus vaccine T-VEC against metastasized melanoma, and Pexa-Vec and PROSTVAC that are currently in clinical trials. Virus-based cancer vaccines have shown encouraging results in numerous studies in enhancing overall survival, relapse-free survival, and overall response rate among patients with solid tumors. This review underscores the necessity for future research aimed at improving the efficacy of virus-based cancer vaccines and investigating combination therapies with other immunotherapies to achieve optimal treatment outcomes.

Novel recombinant vaccinia virus-vectored vaccine affords complete protection against homologous Borrelia burgdorferi infection in mice

ABSTRACT The rising prevalence of Lyme disease (LD) in North America and Europe has emerged as a pressing public health concern. Despite the availability of veterinary LD vaccines, no vaccine is currently available for human use. Outer surface protein C (OspC) found on the outer membrane of the causative agent, Borrelia burgdorferi, has been identified as a promising target for LD vaccine development due to its sustained expression during mammalian infection. However, the efficacy and immunological mechanisms of LD vaccines solely targeting OspC are not well characterized. In this study, we developed an attenuated Vaccinia virus (VV) vectored vaccine encoding type A OspC (VV-OspC-A). Two doses of the VV-OspC-A vaccine conferred complete protection against homologous B. burgdorferi challenge in mice. Furthermore, the candidate vaccine also prevented the development of carditis and lymph node hyperplasia associated with LD. When investigating the humoral immune response to vaccination, VV-OspC-A was found to induce a robust antibody response predominated by the IgG2a subtype, indicating a Th1-bias. Using a novel quantitative flow cytometry assay, we also determined that elicited antibodies were capable of inducing antibody-dependent cellular phagocytosis in vitro. Finally, we demonstrated that VV-OspC-A vaccination generated a strong antigen-specific CD4+ T-cell response characterized by the secretion of numerous cytokines upon stimulation of splenocytes with OspC peptides. This study suggests a promising avenue for LD vaccine development utilizing viral vectors targeting OspC and provides insights into the immunological mechanisms that confer protection against B. burgdorferi infection.

Enhanced Expression of the L1R Gene of Vaccinia Virus by the tPA Signal Sequence Inserted in a Fowlpox-Based Recombinant Vaccine.

The use of Vaccinia virus (VACV) as a preventive vaccine against variola, the etiological agent of smallpox, led to the eradication of smallpox as a human disease. The L1 protein, a myristylated transmembrane protein present on the surface of mature virions, plays a significant role in infection and morphogenesis, is well-conserved in all orthopoxviruses, and is the target of neutralizing antibodies. DNA recombinant vaccines expressing this protein were successfully used, but they showed lower efficacy in non-human and human primates when used alone, and viral-vectored fowlpox vaccines were already proved to increase immunogenicity when used as a boost. Here, we constructed a novel fowlpox-based recombinant (FPtPA-L1R), in which the tissue plasminogen activator signal sequence was linked to the 5' end of the L1R gene to drive the L1 protein into the cellular secretion pathway. FPtPA-L1R expresses a functional heterologous protein that can be immunoprecipitated by hyperimmune rabbit serum. The protein shows cytoplasmic and membrane subcellular localizations and long-lasting expression in CEF, non-human primate Vero and human MRC-5 cells. The tissue plasminogen activator signal sequence can thus contribute significantly to the expression of the L1 protein and may enhance the immunogenicity of a putative DNA/FP prime-boost vaccine.

SARS-CoV-2 Infection Risk Imposed by Fully-vaccinated Air Travelers Attending an Island-confined Quarantine System Enabling Tourism During the Pandemic: A Retrospective Cohort Study.

This study aimed to identify the incidence of SARS-CoV-2 infection among fully vaccinated air travelers participating in an island-confined quarantine system (Phuket Sandbox Program). It also compared the differential risk of SARS-CoV-2 infection across different COVID-19 vaccines and the difference in time-to-detection periods between asymptomatic and symptomatic cases. This retrospective cohort study determined the cumulative incidence of SARS-CoV-2 infection among 63,052 air travelers who participated in a quarantine program from July 1 to October 31, 2021. Using Poisson regression with robust standard errors, we estimated the relative risk of SARS-CoV-2 infection across different brands and types of COVID-19 vaccines, adjusting for relevant covariates. We visualized the time-to-detection periods for SARS-CoV-2 infection using Kaplan-Meier failure curves and compared these curves for asymptomatic and symptomatic travelers using the log-rank test. The overall incidence of SARS-CoV-2 infection was 0.3%. Individuals vaccinated with Ad26.COV2.S, Gam-COVID-Vac, CoronaVac, and replicating viral vector vaccines faced a significantly higher risk of infection than those who received the BNT162b2 and mRNA vaccines. The time-to-detection periods for asymptomatic and symptomatic cases did not differ significantly. Despite the relatively low risk of SARS-CoV-2 infection, a risk of breakthrough cases remained with certain vaccines. Given the high proportion of asymptomatic cases, quarantine and intermittent testing should be implemented. The mandatory quarantine system proved effective in managing positive cases without necessitating a complete shutdown of travel. Implementing an island quarantine could be a viable strategy for reintroducing travel and tourism during a future COVID-19 outbreak or a new pandemic.

Adenovirus-Mediated Expression of Dengue Virus 2 Envelope Ferritin Nanoparticles Induced Virus-Specific Immune Responses in BALB/c Mice

This study provides a preliminary background for the development of a viral vector vaccine for the dengue virus using genetic material encoded by dengue envelope ferritin nanoparticles. Adenoviruses were generated for the recombinant envelope of dengue virus 2 (DENV2) and the envelope human ferritin heavy chain using a two-vector adenovirus system. The primary immunostimulatory activity of the two viruses was analyzed in mice to determine the effect of envelope ferritin nanoparticles. Transfection of a shuttle vector delivered the target gene and packaging vector carrying the packaging signal, and recombinant adenoviruses (rAds) were generated and purified using an ultracentrifugation method. Transduction efficiencies of the generated adenoviruses were confirmed in A549 cells. Purified adenoviruses (8 × 106 PFU/mL) were immunized intramuscularly into 6 weeks old BALB/c mice. Subsequently, the DENV2-specific IgG titer was evaluated 1 and 4 weeks after immunization. Envelope ferritin-immunized mice showed a significant IgG response compared to envelope-only immunized mice at 1 and 4 weeks after immunization, revealing the persistence of the dengue virus-specific IgG response. This method demonstrated the capability of the viral vector vaccine to be used as a carrier for ferritin nanoparticles, instead of direct immunization with ferritin nanoparticles.

Intranasal parainfluenza virus-vectored vaccine expressing SARS-CoV-2 spike protein of Delta or Omicron B.1.1.529 induces mucosal and systemic immunity and protects hamsters against homologous and heterologous challenge.

The continuous emergence of new SARS-CoV-2 variants requires that COVID vaccines be updated to match circulating strains. We generated B/HPIV3-vectored vaccines expressing 6P-stabilized S protein of the ancestral, B.1.617.2/Delta, or B.1.1.529/Omicron variants as pediatric vaccines for intranasal immunization against HPIV3 and SARS-CoV-2 and characterized these in hamsters. Following intranasal immunization, these B/HPIV3 vectors replicated in the upper and lower respiratory tract and induced mucosal and serum anti-S IgA and IgG. B/HPIV3 expressing ancestral or B.1.617.2/Delta-derived S-6P induced serum antibodies that effectively neutralized SARS-CoV-2 of the ancestral and B.1.617.2/Delta lineages, while the cross-neutralizing potency of B.1.1.529/Omicron S-induced antibodies was lower. Despite the lower cross-neutralizing titers induced by B/HPIV3 expressing S-6P from B.1.1.529/Omicron, a single intranasal dose of all three versions of B/HPIV3 vectors was protective against matched or heterologous WA1/2020, B.1.617.2/Delta or BA.1 (B.1.1.529.1)/Omicron challenge; hamsters were protected from challenge virus replication in the lungs, while low levels of challenge virus were detectable in the upper respiratory tract of a small number of animals. Immunization also protected against lung inflammatory response after challenge, with mild inflammatory cytokine induction associated with the slightly lower level of cross-protection of WA1/2020 and B.1.617.2/Delta variants against the BA.1/Omicron variant. Serum antibodies elicited by all vaccine candidates were broadly reactive against 20 antigenic variants, but the antigenic breadth of antibodies elicited by B/HPIV3-expressed S-6P from the ancestral or B.1.617.2/Delta variant exceeded that of the S-6P B.1.1.529/Omicron expressing vector. These results will guide development of intranasal B/HPIV3 vectors with S antigens matching circulating SARS-CoV-2 variants.

The importance of the role of T-cell immunity in the development of modern tick-borne encephalitis vaccines

The tick-borne encephalitis (TBE) virus is highly pathogenic and can affect the central nervous system, leading to severe chronic effects or death. The only effective measure to combat TBE is vaccine prophylaxis. Vaccines that are currently used for mass immunization are based on inactivated TBE virus, they provide a protective immune response, but such vaccines require multiple administrations. A possible reason for short-term immunity is an incomplete functional T-cell response to these types of vaccines. The aim of this review is to analyze the literature on the role of the T-cell immune response in protecting the body from tick-borne encephalitis, its importance for vaccine development, and to consider approaches to the development of new TBE vaccines based on different platforms. When preparing the review, we analyzed the literature presented in scientific databases — PubMed, Scopus, Elsevier, Google Scholar as of April 2024. The following keywords were used for the search: vaccine, tick-borne encephalitis virus, T-cell immune response, flaviviruses. A several publications have demonstrated that T-cell responses following natural infection with TBE virus and after vaccination with inactivated virus are different. During viral infection, both Th1- and Th2-type CD4+ T cells and CD8+ T cells are activated and play an important role in the elimination of viral infection. After vaccination, the only Th2-type CD4+ T-cell response predominates, which may be the reason for the short-lived immune response. To date, a number of different types of experimental TBE vaccines are being studied, such as live-attenuated vaccines, viral vector vaccines, subunit vaccines, virus-like particles, DNA and mRNA vaccines, and polyepitope immunogens. In our opinion, the most promising in terms of T-cell response activation are vaccines based on T-cell polyepitope immunogens delivered in the form of DNA or mRNA.

“Mechanic’s Hand” with Polyarthralgia and Transient Autoimmune Features after COVID Vaccination

Abstract Autoimmune diseases are now well reported with COVID vaccination. Rheumatological, neurological, cardiac, and hematological adverse events are observed globally. Dermatological adverse events are reported in a few cases but dermatological with rheumatological manifestation with reversible autoimmune phenomenon after COVID vaccination is not reported commonly in literature. “Mechanic’s hands” is blackish discoloration of palmar aspects of both hands and knuckles commonly reported in rheumatological autoimmune condition such as dermatomyositis. In this case report, a 28-year-old male presented with polyarthralgia with myalgia and fatigability after 1 month of COVID vaccination. His joint pain symptoms worsened over 4 weeks and developed blackish pigmentation of both hands predominantly involving palms to present as mechanic’s hands. Vasculitis workup was inconclusive and rheumatologic workup documented raised antinuclear antibody titers and rheumatoid factor. We have started him on steroid and hydroxychloroquine and observed satisfactory clinical response with near complete resolution of “mechanic’s hands” in 24 weeks. Mechanic’s hands with rheumatological syndrome which is a rare vaccine-related adverse event, reversible, and easily treatable with routinely available medicines, and importantly it is having excellent prognosis. Mechanic’s hand is first time reported in medical literature after COVID vaccination. Minimal systemic adverse events are known to occur with all viral vector vaccines, but its occurrence is rare and it should not impact on routine vaccinations, as vaccination is a key step in this pandemic to protect humankind.

Methodical and Immunological Insights of Prime COVID-19 Vaccines

Abstract:: Vaccines' discovery, manufacturing, and distribution have been on a historic uptick in response to this worldwide COVID-19 pandemic. A handful of vaccines have been approved on an emergency basis after passing minimal clinical trials. There are voids in the existing body of research and the published body of work on phase II and III clinical trial outcomes, efficacy, and recently developed side effects of the approved COVID-19 vaccines. Furthermore, the immunological and methodological insights of successful vaccinations are still unpopular and are not publicly reported. We have attempted to review some major classes of COVID-19 vaccines, namely inactivated viral particle vaccine (BBV152 - Covaxin), mRNA vaccines (BNT162b2 - Pfizer and mRNA-1273- Moderna), viral vector vaccines (Gam-COVID-Vac-Sputnik and ChAdOx1-S-Astrazeneca) and protein subunit vaccine (NVX-CoV2373-Novavax) and discuss their methodological and immunological formulations. This review intends to address the existing literature's gaps and limitations and the vaccine’s safety, efficiency, and effectiveness profiles. This report, by accumulating and comparing the existing publicly available literature and datasheets of the vaccines, concludes that the efficacy of the vaccinations has been found to be 81% for BBV152 (COVAXIN), 94.5% for BNT162b2 (Pfizer), 94.5% for mRNA-1273 (Moderna), 91.6% for Gam-COVID-Vac (Sputnik V), 62–90% for ChAdOx1-S (AstraZeneca), and 96.4% for NVX-CoV2373 (Novavax), demonstrating their efficacy in lowering the severity and frequency of SARS-CoV-2 infection. We conclude that while the commercially approved vaccines have a few limitations regarding clinical trials and side effects, they provide immunity with efficacy ranging from 81% to 96.4% against COVID-19.

The progress of tumor vaccines clinical trials in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains a significant global health challenge, with high mortality rates and limited treatment options. Tumor vaccines have emerged as a potential therapeutic approach, aiming to stimulate the immune system to specifically target tumor cells. This study screened 283 clinical trials registered on ClinicalTrials.gov through July 31, 2023. After excluding data that did not meet the inclusion criteria, a total of 108 trials were assessed. Data on registered number, study title, study status, vaccine types, study results, conditions, interventions, outcome measures, sponsor, collaborators, drug target, phases, enrollment, start date, completion date and locations were extracted and analyzed. The number of vaccines clinical trials for NSCLC has continued to increase in recent years, the majority of which were conducted in the United States. Most of the clinical trials were at stages ranging from Phase I to Phase II. Peptide-based vaccines accounted for the largest proportion. Others include tumor cell vaccines, DNA/RNA vaccines, viral vector vaccines, and DC vaccines. Several promising tumor vaccine candidates have shown encouraging results in early-phase clinical trials. However, challenges such as heterogeneity of tumor antigens and immune escape mechanisms still need to be addressed. Tumor vaccines represent a promising avenue in the treatment of NSCLC. Ongoing clinical trials are crucial for optimizing vaccine strategies and identifying the most effective combinations. Further research is needed to overcome existing limitations and translate these promising findings into clinical practice, offering new hope for NSCLC patients.

Influenza Vaccine Effectiveness and Progress Towards a Universal Influenza Vaccine.

At various times in recent decades, surges have occurred in optimism about the potential for universal influenza vaccines that provide strong, broad, and long-lasting protection and could substantially reduce the disease burden associated with seasonal influenza epidemics as well as the threat posed by pandemic influenza. Each year more than 500 million doses of seasonal influenza vaccine are administered around the world, with most doses being egg-grown inactivated subunit or split-virion vaccines. These vaccines tend to have moderate effectiveness against medically attended influenza for influenza A(H1N1) and influenza B, and somewhat lower for influenza A(H3N2) where differences between vaccine strains and circulating strains can occur more frequently due to antigenic drift and egg adaptations in the vaccine strains. Several enhanced influenza vaccine platforms have been developed including cell-grown antigen, the inclusion of adjuvants, or higher antigen doses, to improve immunogenicity and protection. During the COVID-19 pandemic there was unprecedented speed in development and roll-out of relatively new vaccine platforms, including mRNA vaccines and viral vector vaccines. These new platforms present opportunities to improve protection for influenza beyond existing products. Other approaches continue to be explored. Incremental improvements in influenza vaccine performance should be achievable in the short to medium term.

Exploring the adverse events of Oxford–AstraZeneca, Pfizer-BioNTech, Moderna, and Johnson and Johnson COVID-19 vaccination on Guillain–Barré Syndrome

The vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an important public health strategy to prevent people from the pandemic. Vaccines are a game-changing tool, it is essential to understand the adverse events after COVID-19 vaccination. This study explored the adverse events of COVID-19 Vaccination Oxford–AstraZeneca, Pfizer-BioNTech, Moderna, Johnson and Johnson on Guillain–Barré Syndrome (GBS). In this study, initially 128 documents were identified from the databases, including Pub-Med, Web of Science-Clarivate Analytics, Scopus, and Google Scholar. The articles on COVID-19 vaccination and GBs were searched using the keywords “SARS-CoV-2, COVID-19, Vaccination, and Guillain Barré Syndrome, GBS”, finally, 16 documents were included in the analysis and synthesis. After administering 1,680,042,214 doses of COVID-19 vaccines, 6177 cases were identified with 10.5 cases per million vaccine doses. A significant positive risk was found between COVID-19 vaccine administration and GBS with a risk rate of RR 1.97 (95% CI 1.26–3.08, p = 0.01). The mRNA vaccines were associated with 2076 cases, and 1,237,638,401 vaccine doses were linked with 4.47 GBS events per million vaccine doses. The first dose of the m-RNA vaccine was associated with 8.83 events per million doses compared to the second dose with 02 events per million doses. The viral-vector vaccine doses 193,535,249 were linked to 1630 GBS cases with 11.01 cases per million doses. The incidence of GBS after the first dose was 17.43 compared to 1.47 cases per million in the second dose of the viral-vector vaccine. The adverse events of the Oxford–AstraZeneca vaccine were linked to 1339 cases of GBS following 167,786,902 vaccine doses, with 14.2 cases per million doses. The Oxford–AstraZeneca vaccine significantly increased the risk of GBS RR: 2.96 (95% CI 2.51–3.48, p = 0.01). For the Pfizer-BioNTech vaccine, there were 7.20 cases per million doses of the vaccine, and no significant association was identified between the Pfizer-BioNTech vaccine and GBS incidence RR: 0.99 (95% CI 0.75–1.32, p = 0.96). Moderna vaccine was related with 419 cases of GBS after administering 420,420,909 doses, with 2.26 cases per million doses. However, Johnson and Johnson's vaccination was linked to 235 GBS after 60,256,913 doses of the vaccine with 8.80 cases per million doses. A significant association was seen between the risk of GBS and Ad.26.COV2. S vaccine, RR: 2.47 (95% CI 1.30–4.69, p < 0.01). Overall, a significant association was seen between the COVID-19 vaccines and the risk of GBS. The incidence of GBS was higher after the first dose compared to GBS cases per million in the second dose.

Vaccination of cattle with a virus vector vaccine against a major membrane protein of Mycobacterium avium subsp. paratuberculosis elicits CD8 cytotoxic T cells that kill intracellular bacteria

Analysis of the recall response ex vivo in cattle vaccinated with a Mycobacterium avium subsp. paratuberculosis (Map) rel deletion mutant revealed the immune response was directed toward a 35 kD major membrane protein (MMP) of Map. Antigen presenting cells (APC) primed with MMP elicited expansion of CD8 cytotoxic memory T cells (CTL) with ability to kill intracellular bacteria. Development of CTL was MHC-restricted. The gene MAP2121c, encoding MMP, was modified for expression of MMP (tPA-MMP-2mut) in a mammalian cell line to explore the potential of developing MMP as a vaccine. Ex vivo stimulation of PBMC, from Map free cattle, with APC primed with tPA-MMP-2mut expressed p35 elicited a primary CD8 CTL response comparable to the recall response elicited with PBMC from cattle vaccinated with either the Maprel deletion mutant or MMP. In the present study, the modified gene for MMP, now referred to as p35NN, was placed into a bovine herpes virus-4 (BoHV4) vector to determine the potential use of BoHV-4AΔTK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4AΔTK-p35NN elicited a CTL recall response, as detected ex vivo. The results show use of a virus vector is an effective way for delivery of MMP as a vaccine. The immunogenic activity of MMP was not lost when modified for expression in mammalian cells. The next step is to conduct a field trial to determine if presence of an immune response to MMP prevents Map from establishing an infection.

Improved thermal stabilization of VSV-vector with enhanced vacuum drying in pullulan and trehalose-based films

One major limitation of effective vaccine delivery is its dependency on a robust cold chain infrastructure. While Vesicular stomatitis virus (VSV) has been demonstrated to be an effective viral vaccine vector for diseases including Ebola, its −70 °C storage requirement is a significant limitation for accessing disadvantaged locations and populations. Previous work has shown thermal stabilization of viral vaccines with a combination of pullulan and trehalose (PT) dried films. To improve the thermal stability of VSV, we optimized PT formulation concentrations and components, as well as drying methodology with enhanced vacuum drying. When formulated in PT films, VSV can be stored for 32 weeks at 4 °C with less than 2 log PFU loss, at 25 °C with 2.5 log PFU loss, and at 37 °C with 3.1 log PFU loss. These results demonstrate a significant advancement in VSV thermal stabilization, decreasing the cold chain requirements for VSV vectored vaccines.

Safety pharmacology of human endogenous retrovirus-enveloped baculoviral DNA vaccines against SARS-CoV-2 in Sprague-Dawley rats and beagle dogs

The coronavirus disease 2019 (COVID-19) emerged as a major global health crisis, posing significant health, economic, and social challenges. Vaccine development has been a crucial response to the severe-acute-respiratory-syndrome-related coronavirus-2 pandemic owing to the critical role of immunization in controlling infectious diseases, leading to the expedited development of several effective vaccines. Although mRNA platform-based COVID-19 vaccines authorized under emergency-use authorization have been administered globally, concerns regarding the vaccines have increased owing to the occurrence of various side effects. The present study aimed to evaluate the safety of a non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) vaccine encoding SARS-CoV-2 antigens. Owing to the limited number of existing safety pharmacology studies on AcHERV as a viral vector vaccine, we conducted neurobehavior (Modified Irwin’s Test), body temperature, and respiratory function studies in rats and cardiovascular system studies in male beagle dogs, which were administered the AcHERV-COVID-19 vaccine using telemetry. The safety assessment revealed no significant toxicological alterations. However, in rats, both sexes administered with the AcHERV-COVID-19 vaccine exhibited a temporary increase in body temperature, which normalized or showed signs of recovery. In conclusion, AcHERV-COVID-19 demonstrates a sufficient safety profile that supports its potential evaluation in future clinical trials.

Recent research advances in the development of Dabie Banda virus vaccines.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.

A Simple and Versatile Method for Ex Vivo Monitoring of Goat Vaginal Mucosa Transduction by Viral Vector Vaccines.

Goat may represent a valid large animal model for human pathogens and new vaccines testing. Appropriate vaccine administration is a critical component of a successful immunization program. The wrong route of administration may reduce the efficacy of the vaccine, whereas the proper administration strategy can enhance it. Viral vectors have been employed successfully for goat and sheep immunization; however, no data concerning the vaginal route are available. A viral vector's ability to transduce the site of inoculation is of primary interest. In this study, a fast and reliable ex vivo assay for testing the transduction capability of an Ad5-based vector when intravaginally administered was developed. An Ad5 vector delivering an expression cassette with a bicistronic reporter gene, Ad5-CMV-turboGFP-IRES-Luc2, was constructed. We demonstrated Ad5-CMV-turboGFP-IRES-Luc2's ability to transduce caprine vaginal mucosa by ex vivo bioluminescent imaging (BLI) employing a simple CCD camera apparatus for chemiluminescence western immunoblotting. These data, though simple, provide valuable insights into developing a vaginal immunization strategy using a viral vector-based vaccine to protect against pathogens causing genital diseases.