Vaccinia Virus Vectors Research Articles

Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys

Background/Objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved. Methods: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors. Results: rLC16m8-mcl2.2 hemagglutinin (HA) and rLC16m8-mcl2.3.4 HA consisted of a recombinant LC16m8 vector encoding the HA protein from clade 2.2 or clade 2.3.4 viruses (respectively); rDIs-mcl2.2 HA consisted of a recombinant DIs vector encoding the HA protein from clade 2.2. A single dose of rLC16m8-mcl2.2 HA showed rapid (1 week after vaccination) and long-term protection (20 months post-vaccination) in mice against the HPAI H5N1 virus. Moreover, cynomolgus macaques immunized with rLC16m8-mcl2.2 HA exhibited long-term protection when challenged with a heterologous clade of the HPAI H5N1 virus. Although the DIs strain is unable to grow in most mammalian cells, rDIs-mcl2.2 HA also showed rapid and long-lasting effects against HPAI H5N1 virus infection. Notably, the protective efficacy of rDIs-mcl2.2 HA was comparable to that of rLC16m8-mcl2.2 HA. Furthermore, these vaccines protected animals previously immunized with VACVs from a lethal challenge with the HPAI H5N1 virus. Conclusions: These results suggest that both rLC16m8-mcl2.2 HA and rDIs-mcl2.2 HA are effective in preventing HPAI H5N1 virus infection, and rDIs-mcl2.2 HA is a promising vaccine candidate against H5 HA-subtype viruses.

Strategic and Technical Considerations in Manufacturing Viral Vector Vaccines for the Biomedical Advanced Research and Development Authority Threats

Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority’s vaccine portfolio.

Different COVID-19 vaccines and their respective technological platforms: systematic review of clinical trials

Introduction: The COVID-19 pandemic has highlighted the importance of vaccination in reducing severe cases and deaths. However, the emergence of new SARS-CoV-2 variants raises concerns about the efficacy and safety of available vaccines, mainly due to the diversity of technological platforms used in their development. Objectives: To elucidate the current knowledge about the main vaccine against COVID-19 and their respective technological platforms, licensed and in the licensing phase. Methods: Systematic review according to the PRISMA statement of articles published from 2020, through the PubMed database. Results: The search resulted in fifty studies, of which twenty-one were included. Clinical trials addressed vaccines that use mRNA platforms (n=4), non-replicant viral vector (n=3), attenuated virus (n=2), inactivated vaccine (n=1), recombinant protein nanoparticles (n=3), vaccine using virus-like particles (n=1), subunit vaccine (n=1), DNA vaccine (n=1). Most of the vaccines showed good tolerability and induced neutralizing antibodies against various variants of SARS-CoV-2. Conclusions: Except for the non-replicant viral vector vaccine, intranasal ChAdOx1 nCoV-19 that did not induce mucosal and systemic immune responses, and the DNA vaccine, which induced only a good cellular response, the other vaccines demonstrated good tolerability and efficacy in inducing immune responses.

A Bibliometric Analysis on Multi-epitope Vaccine Development Against SARS-CoV-2: Current Status, Development, and Future Directions.

The etiological agent for the coronavirus disease 2019 (COVID-19), the SARS-CoV-2, caused a global pandemic. Although mRNA, viral-vectored, DNA, and recombinant protein vaccine candidates were effective against the SARS-CoV-2 Wuhan strain, the emergence of SARS-CoV-2 variants of concern (VOCs) reduced the protective efficacies of these vaccines. This necessitates the need for effective and accelerated vaccine development against mutated VOCs. The development of multi-epitope vaccines against SARS-CoV-2 based on in silico identification of highly conserved and immunogenic epitopes is a promising strategy for future SARS-CoV-2 vaccine development. Considering the evolving landscape of the COVID-19 pandemic, we have conducted a bibliometric analysis to consolidate current findings and research trends in multi-epitope vaccine development to provide insights for future vaccine development strategies. Analysis of 102 publications on multi-epitope vaccine development against SARS-CoV-2 revealed significant growth and global collaboration, with India leading in the number of publications, along with an identification of the most prolific authors. Key journals included the Journal of Biomolecular Structure and Dynamics, while top collaborations involved Pakistan-China and India-USA. Keyword analysis showed a prominent focus on immunoinformatics, epitope prediction, and spike glycoprotein. Advances in immunoinformatics, including AI-driven epitope prediction, offer promising avenues for the development of safe and effective multi-epitope vaccines. Immunogenicity may be further improved through nanoparticle-based systems or the use of adjuvants along with real-time genomic surveillance to tailor vaccines against emerging variants.

Protection induced by recombinant vaccinia virus targeting the ROP4 of Toxoplasma gondii in mice.

Toxoplasmosis is a parasitic disease affecting a significant portion of the global population, whose etiology can be attributed to the protozoan organism Toxoplasma gondii. Despite its public health importance, an efficacious vaccine to prevent human toxoplasmosis remains unavailable. To this end, we designed an experimental toxoplasmosis vaccine using recombinant vaccinia virus vectors (rVacv) expressing the T. gondii rhoptry protein 4 (ROP4) antigen and evaluated its efficacy in a murine model. Intranasal vaccination with ROP4-rVacvs induced parasite-specific serum antibody responses as early as 3 weeks post-immunization, with subsequent immunizations elevating antibody responses to a greater extent. When challenged with T. gondii ME49 strain, significantly enhanced levels of mucosal IgA antibodies were detected in the intestines of immunized mice. Additionally, ROP4-rVacv immunization ensured that T cells and germinal center B cell populations were retained at high levels. These immune responses mitigated the severity of neuroinflammation, reduced tissue cyst formation, and ensured the survival of immunized mice. Our findings indicate that ROP4-rVacv could be a promising toxoplasmosis vaccine candidate.

Immunogenic recombinant Mayaro virus-like particles present natively assembled glycoprotein

AbstractVirus-like particles (VLPs) are an established vaccine platform and can be strong immunogens capable of eliciting both humoral and cellular immune responses against a range of pathogens. Here, we show by cryo-electron microscopy that VLPs of Mayaro virus, which contain envelope glycoproteins E1-E2 and capsid, exhibit an architecture that closely resembles native virus. In contrast to monomeric and soluble envelope 2 (E2) glycoprotein, both VLPs as well as the adenovirus and modified vaccinia virus Ankara (MVA) vaccine platforms expressing the equivalent envelope glycoproteins E1-E2, and capsid induced highly neutralising antibodies after immunisation. The levels of neutralising antibodies elicited by the viral-vectored vaccines of structural proteins and VLPs increased significantly upon boosting. Immunisation of Mayaro virus VLPs in mice with or without an adjuvant (poly:IC) yielded similar levels of neutralising antibodies suggesting that the VLPs may be used for immunisation without the need for an adjuvant. A single or two doses of non-adjuvanted 5 µg of MAYV VLP vaccination provided significant protection against viremia and MAYV-induced foot swelling in the C57BL/6 mouse challenge model. MAYV VLPs represent a non-infectious vaccine candidate, which may constitute a complementary option for future immunisation strategies against this important emerging alphavirus.

Newcastle Disease Virus-Vectored African Swine Fever Virus Antigen Cocktail Delays the Onset of ASFV-SY18 but Is Not Protective.

African Swine Fever (ASF) is a highly contagious viral disease threatening the global pig industry. Currently, only two gene-deleted live attenuated vaccines are approved, exclusively in Vietnam, and their long-term effectiveness and safety are unproven, prompting the need for safer alternatives. This study assessed a cocktail of African Swine Fever Virus (ASFV) antigens delivered via a recombinant Newcastle Disease Virus (rNDV) vector against the genotype II ASFV-SY18. Antigens pB602L, pEP84R, and p22 (pKP177R) were selected based on virus neutralization and lymphocyte proliferation assays in mice and combined with capsid protein p72 (pB646L) for vaccination and challenge in pigs. The antigen cocktail delayed ASF symptoms by 3-4 days but did not prevent the lethal ASFV-SY18 infection. Significant ASFV-specific gamma interferon (IFN-γ) positive responses and NDV antibodies were detected post-inoculation, showing an induced immune response, though ASFV-specific p72 antibodies were absent. The cocktail did not cause cytokine imbalance, indicating the vector's safety in pigs. Despite some delay in disease progression, the protection against genotype II ASFV was inadequate, underscoring the need to select more effective antigens and enhance immune responses for virus-vectored vaccines.

Immunization against COVID-19: A Comprehensive Review on the Leading Vaccines

Abstract: The global impact of coronavirus disease (COVID-19) has prompted researchers and scientists to develop effective vaccines to contain the spread of the pandemic. This has led to the deployment of a range of vaccines from different pharmaceutical companies across the globe in a very short span of time. The current article provides a comprehensive record of all the vaccines developed against coronavirus with a specific focus on the mode of action and administration of the vaccines. The article also dwells on the composition, possible side effects and criteria for the choice of individuals for the administration of the vaccines. Vaccines against COVID-19 have been broadly categorized as mRNA vaccines, adenoviral vector-based vaccines and inactivated vaccines. Among the mRNA vaccines, the Pfizer vaccine and Moderna vaccines gained significant popularity. The Oxford Astro Zeneca vaccine and Sputnik V were the most effective viral vector vaccines. Inactivated vaccines such as Covaxin and Sinovac were also significant contributions to contain the pandemic. The review discusses the efficiency of vaccines against the variants of SARS CoV2. The review will provide a clear-cut idea about all kinds of exciting vaccines against COVID-19. At present, where the immediate crisis of the pandemic has been successfully contained, this article acts as a resource for future public health endeavors, policy makers, health care professionals and the general public to understand the diversity of COVID-19 vaccines.

Longitudinal Immunological Analysis of Portuguese Healthcare Workers Across the COVID-19 Pandemic Reveals Differences in the Humoral Immune Response to Vaccines.

Background: A vaccination programme against severe acute respiratory syndrome coronavirus 2 was initiated in Portugal in December 2020. In this study, we report the findings of a prospective cohort study implemented with the objective of monitoring antibody production in response to COVID-19 vaccination. Methods: The humoral immune response to vaccination was followed up using blood samples collected from 191 healthcare workers. Participants were split into three groups: the Oxford-AstraZeneca (Vaxzevria) vaccine group (n = 68), the Pfizer-BioNTech COVID-19 (Comirnaty) vaccine group (n = 51), and the Post-COVID group (n = 72). The kinetics of anti-spike antibody production were evaluated until 56 days on average after the third dose (booster). Results: We observed that antibody titres peaked approximately one month after full vaccination and declined steadily thereafter. We also found that mRNA vaccination induces higher titres of antibodies than viral vector vaccination, and both generate greater antibody responses than mild or moderate COVID-19. Additionally, whilst the booster for the Oxford-AstraZeneca and Pfizer-BioNTech groups led to antibody levels higher than those at any previous sample collection point, the booster for the Post-COVID group (persons with a history of COVID-19 prior to vaccination) led to antibody levels lower than those attained one month after the second dose. Interpretation: Our results indicate that there are different kinetics of antibody production between individuals who received the Pfizer-BioNtech mRNA vaccine and those who received the Oxford-AstraZeneca vector vaccine, or individuals who had COVID-19 before being vaccinated. Additionally, we observed that exposure to either natural infection or vaccination modulates the response to subsequent vaccination. This is particularly evident after administration of the third dose to the Post-COVID group, where our findings point to a hindrance in vaccine boosting, probably due to unwanted feedback by high titres of pre-existing antibodies.

A mini-review on the side-effects of COVID-19 vaccines on Thrombosis with Thrombocytopenia Syndrome (TTS)

In May 2024, the well-known pharmaceutical company AstraZeneca admitted that its COVID - 19 (SARS-CoV-2) vaccine can cause the rare side effect of Thrombosis with Thrombocytopenia Syndrome (TTS), involving blood clots along with a low platelet count. This is a potentially severe condition, with a fatality rate up to 44%. Several studies indicate a link between different COVID-19 vaccines and TTS or VITT (Vaccine Induced Thrombotic Thrombocytopenia), however, a majority of such cases have been reported after the vaccines ChAdOx1 nCoV-19, manufactured by AstraZeneca and Oxford University, and Ad26.COV2.S, made by Johnson and Johnson. Both these vaccines use the same mechanism: modified adenovirus vectors. In these viral vector vaccines, some researchers have theorized that an immune response could be triggered where the body produces antibodies against platelet factor 4 (PF4), a protein involved in blood clotting. Another theory suspects endothelial cells and receptors to have an inflammatory response, causing VITT. Though the exact cause remains unknown, an association between some vaccines and thrombotic events can definitely be discerned by past research, so this article will evaluate different vaccines and their connections with such events.

Review on Various Type of Vaccines for Controlling Infectious Disease

Background: Vaccines have played a critical role in the prevention and treatment of infectious diseases, greatly lowering worldwide morbidity and mortality. This review examines many forms of vaccinations. In contrast, inactivated vaccines, such as the polio vaccine, are safer for immunocompromised people, they frequently require booster shots. Aim: This review emphasises the importance of vaccinations in public health and the need for innovation to tackle future infectious disease threats. The introduction of new pathogens has prompted the creation of novel vaccination platforms, including mRNA and viral vector vaccines. mRNA vaccines, such as those used to treat COVID-19, use genetic instructions to direct cells to manufacture antigens, resulting in strong immunity. Conclusion: These vaccines have demonstrated excellent efficacy and rapid scaling, making them valuable instruments in pandemics. This review emphasises the necessity of designing vaccine methods that meet individual illnesses, demographics, and logistical obstacles. While vaccinations have considerably reduced the occurrence of infectious diseases, more research is needed to address future threats, improve vaccine efficacy, and overcome obstacles such as vaccine reluctance and global inequities. Understanding the capabilities and limits of each vaccine type will help researchers and policymakers better equip healthcare systems to address current and future infectious disease concerns.

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.

Development of adeno-associated virus vector vaccines

Development of adeno-associated virus vector vaccines

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 severe acute respiratory syndrome coronavirus 2 (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 coronavirus disease 2019 (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, 2021 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.