Innovative Vaccine Research Articles

Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.

HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance and incomplete response remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for the management of dyslipidemia by enhancing the clearance of low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 and cancer cells. We present an innovative immunization approach combining capsid virus-like particle (cVLP)-based vaccines against HER2 and PCSK9. The therapeutic activity of the combined vaccine was evaluated in female mice challenged with HER2-positive mammary carcinoma cells. Controls included untreated mice and mice treated with cVLP-PCSK9 and cVLP-HER2 as standalone therapies. Antibodies elicited by vaccinations were detected through ELISA immunoassay. The functional activity of the antibodies was tested in 3D-soft agar assay on human HER2 + + + trastuzumab sensitive and resistant cells. Mice vaccinated with cVLP-HER2 + cVLP-PCSK9 displayed tumor regression from the 40th day after cell challenge in 100% of mice remaining tumor-free even 4months later. In contrast, 83% of mice treated with cVLP-HER2 vaccine alone experienced an initial tumor regression, followed by tumor relapse in 60% of subjects. Untreated mice and mice treated with the cVLP-PCSK9 vaccine alone developed progressive tumors within 1-2months after cell injection. The combined vaccine approach elicited strong anti-human HER2 antibody responses (reaching 1-2mg/ml range) comprising multiple immunoglobulins isotypes. cVLP-PCSK9 vaccine elicited anti-PCSK9 antibody responses, resulting in a marked reduction in PCSK9 serum levels. Although the anti-PCSK9 response was reduced when co-administered with cVLP-HER2, it remained significant. Moreover, both cVLP-HER2 + cVLP-PCSK9 and cVLP-HER2 alone induced anti-HER2 antibodies able to inhibit the 3D growth of human HER2 + + + BT-474 and trastuzumab-resistant BT-474 C5 cells. Strikingly, antibodies elicited by the combined vaccination were more effective than those elicited by the cVLP-HER2 vaccine alone in the inhibition of trastuzumab-resistant C5 cells. The results indicate that cVLP-PCSK9 vaccination shows adjuvant activity when combined with cVLP-HER2 vaccine, enhancing its therapeutic efficacy against HER2-positive breast cancer and holding promise in overcoming the challenges posed by resistance and incomplete responses to HER2-targeted therapy.

Editorial: Building public confidence in innovative mRNA vaccines

Editorial: Building public confidence in innovative mRNA vaccines

Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from Pseudomonas aeruginosa.

The bacterium Pseudomonas aeruginosa is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, it is currently unclear how OMVs from P. aeruginosa (PA-OMVs) affect lung epithelial cells and their impact on oxidative stress, autophagy, and other physiological activities of lung epithelial cells. In this study, we found that PA-OMVs activated oxidative stress and autophagy in cells. We demonstrated that the NLRP3 (NLR family, pyrin domain containing 3) inhibitor MCC950 can enhance autophagy induced by PA-OMVs. The main function of NLRP3 is related to the body's immune response and inflammation regulation. MCC950 is the most common inhibitor of NLRP3. Additionally, we showed that PA-OMVs not only enhanced the expression of AMP-activated protein kinase, a key regulator of cellular energy homeostasis, and reactive oxygen species, which play a crucial role in cellular signaling and oxidative stress, but also significantly enhanced the expression of NLRP3. Inhibiting the expression of NLRP3 further enhanced the process of PA-OMVs induced autophagy. These results demonstrate that PA-OMVs activate both autophagy and the NLRP3 inflammasome, with NLRP3 suppressing autophagy to a certain extent, hoping to provide broad ideas for the future applications of PA-OMVs.IMPORTANCEThe discovery that lung epithelial cells exposed to outer membrane vesicles from Pseudomonas aeruginosa (PA-OMVs) activate cellular autophagy and induce protective immunity is significant. Specifically, the addition of an NLRP3 inhibitor, MCC950, has been found to decrease NLRP3 targets while simultaneously enhancing the autophagy activity induced by PA-OMVs. This finding unveils a novel theoretical framework for the development of PA-OMVs vaccines, highlighting new targets for enhancing the body's anti-infective responses. By elucidating the mechanisms through which PA-OMVs trigger autophagy and bolster immune defenses, this research opens avenues for innovative vaccine design strategies aimed at combatting infections effectively.

Revolutionizing Nanovaccines: A New Era of Immunization

Infectious diseases continue to pose a significant global health threat. To combat these challenges, innovative vaccine technologies are urgently needed. Nanoparticles (NPs) have unique properties and have emerged as a promising platform for developing next-generation vaccines. Nanoparticles are revolutionizing the field of vaccine development, offering a new era of immunization. They allow the creation of more effective, stable, and easily deliverable vaccines. Various types of NPs, including lipid, polymeric, metal, and virus-like particles, can be employed to encapsulate and deliver vaccine components, such as mRNA or protein antigens. These NPs protect antigens from degradation, target them to specific immune cells, and enhance antigen presentation, leading to robust and durable immune responses. Additionally, NPs can simultaneously deliver multiple vaccine components, including antigens, and adjuvants, in a single formulation, simplifying vaccine production and administration. Nanovaccines offer a promising approach to combat food- and water-borne bacterial diseases, surpassing traditional formulations. Further research is needed to address the global burden of these infections. This review highlights the potential of NPs to revolutionize vaccine platforms. We explore their mechanisms of action, current applications, and emerging trends. The review discusses the limitations of nanovaccines, innovative solutions and the potential role of artificial intelligence in developing more effective and accessible nanovaccines to combat infectious diseases.

Exploring Future Pandemic Preparedness Through the Development of Preventive Vaccine Platforms and the Key Roles of International Organizations in a Global Health Crisis.

Background: The emergence of more than 40 new infectious diseases since the 1980s has emerged as a serious global health concern, many of which are zoonotic. In response, many international organizations, including the US Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), and the European Center for Disease Prevention and Control (ECDC), have developed strategies to combat these health threats. The need for rapid vaccine development has been highlighted by Coronavirus disease 2019 (COVID-19), and mRNA technology has shown promise as a platform. While the acceleration of vaccine development has been successful, concerns have been raised about the technical limits, safety, supply, and distribution of vaccines. Objective: This study analyzes the status of vaccine platform development in global pandemics and explores ways to respond to future pandemic crises through an overview of the roles of international organizations and their support programs. It examines the key roles and partnerships of international organizations such as the World Health Organization (WHO), vaccine research and development expertise of the Coalition for Epidemic Preparedness Innovations (CEPI), control of the vaccine supply chain and distribution by the Global Alliance for Vaccines and Immunization (GAVI), and technology transfer capabilities of the International Vaccine Institute (IVI) in supporting the development, production, and supply of vaccine platform technologies for pandemic priority diseases announced by WHO and CEPI and analyzes their vaccine support programs and policies to identify effective ways to rapidly respond to future pandemics caused by emerging infectious diseases. Methods: This study focused on vaccine platform technology and the key roles of international organizations in the pandemic crisis. Literature data on vaccine platform development was collected, compared, and analyzed through national and international literature data search sites, referring to articles, journals, research reports, publications, books, guidelines, clinical trial data, and related reports. In addition, the websites of international vaccine support organizations, such as WHO, CEPI, GAVI, and IVI, were used to examine vaccine support projects, initiatives, and collaborations through literature reviews and case study methods. Results: The COVID-19 pandemic brought focus on the necessity for developing innovative vaccine platforms. Despite initial concerns, the swift integration of cutting-edge development technologies, mass production capabilities, and global collaboration have made messenger RNA (mRNA) vaccines a game-changing technology. As a result of the successful application of novel vaccine platforms, it is important to address the remaining challenges, including technical limits, safety concerns, and equitable global distribution. To achieve this, it is essential to review the regulatory, policy, and support initiatives that have been implemented in response to the COVID-19 pandemic, with particular emphasis on the key stages of vaccine development, production, and distribution, to prepare for future pandemics. An analysis of the status of vaccine development for priority pandemic diseases implies the need for balanced vaccine platform development. Also, international organizations such as WHO, CEPI, GAVI, and IVI play key roles in pandemic preparedness and the development and distribution of preventive vaccines. These organizations collaborated to improve accessibility to vaccines, strengthen the global response to infectious diseases, and address global health issues. The COVID-19 pandemic response demonstrates how the synergistic collaboration of WHO's standardized guidelines, CEPI's vaccine research and development expertise, GAVI's control of the vaccine supply chain and distribution, and IVI's technology transfer capabilities can be united to create a successful process for vaccine development and distribution. Conclusions: In preparation for future pandemics, a balanced vaccine platform development is essential. It should include a balanced investment in both novel technologies such as mRNA and viral vector-based vaccines and traditional platforms. The goal is to develop vaccine platform technologies that can be applied to emerging infectious diseases efficiently and increase manufacturing and distribution capabilities for future pandemics. Moreover, international vaccine support organizations should play key roles in setting the direction of global networking and preparing for international vaccine support programs to address the limitations of previous pandemic responses. As a result, by transforming future pandemic threats from unpredictable crises to surmountable challenges, it is expected to strengthen global health systems and reduce the social and economic burden of emerging infectious diseases in the long term.

Development of nucleic acid-based vaccines against dengue and other mosquito-borne flaviviruses: the past, present, and future.

Due to their widespread geographic distribution and frequent outbreaks, mosquito-borne flaviviruses, such as DENV (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), and West Nile virus (WNV), are considered significant global public health threats and contribute to dramatic socioeconomic imbalances worldwide. The global prevalence of these viruses is largely driven by extensive international travels and ecological disruptions that create favorable conditions for the breeding of Aedes and Culex species, the mosquito vectors responsible for the spread of these pathogens. Currently, vaccines are available for only DENV, YFV, and JEV, but these face several challenges, including safety concerns, lengthy production processes, and logistical difficulties in distribution, especially in resource-limited regions, highlighting the urgent need for innovative vaccine approaches. Nucleic acid-based platforms, including DNA and mRNA vaccines, have emerged as promising alternatives due to their ability to elicit strong immune responses, facilitate rapid development, and support scalable manufacturing. This review provides a comprehensive update on the progress of DNA and mRNA vaccine development against mosquito-borne flaviviruses, detailing early efforts and current strategies that have produced candidates with remarkable protective efficacy and strong immunogenicity in preclinical models. Furthermore, we explore future directions for advancing nucleic acid vaccine candidates, which hold transformative potential for enhancing global public health.

Advancing novel veterinary vaccines: From comprehensive antigen and adjuvant design to preparation process optimization.

Vaccination stands as the paramount and cost-effective strategy for the prevention and management of animal infectious diseases. With the advances in biological technology, materials science and industrial optimization, substantial progress has been made in the development of innovative veterinary vaccines. A majority of the novel vaccines under current investigation tend to stimulate multiple immune pathways and to achieve long-term resistance against infectious diseases, yet it remains imperative to concentrate research efforts on the efficient utilization of vaccines, mitigating toxic side effects, and ensuring safe production processes. This article presents an overview of research progress in veterinary vaccines, encompassing comprehensive antigen design, adjuvant formulation advancements, preparation process optimization, and rigorous immune efficacy evaluation. It summarizes cutting-edge vaccines derived from in vitro synthesis and in vivo application, emphasizing immunogenic components and immune response mechanisms. It also highlights novel biological adjuvants that enhance immune efficacy, diversify raw materials, and possess targeted functions, while comprehensively exploring advancements in production methodologies and compatible vaccine products. By establishing a foundation for the integrated use of these innovative veterinary vaccines, this work facilitates future interdisciplinary cooperation in their advancement, aiming to accelerate the achievement of herd immunity through concerted efforts.

Towards developing multistrain PEDV vaccines: Integrating basic concepts and SARS-CoV-2 pan-sarbecovirus strategies.

Porcine epidemic diarrhea virus (PEDV) is a major pathogen impacting the global pig industry, with outbreaks causing significant financial losses. The genetic variability of PEDV has posed challenges for vaccine development since its identification in the 1970s, a problem that intensified with its global emergence in the 2010s. Since current vaccines provide limited cross-protection against PEDV strains, and the development of multistrain PEDV vaccines remains an underexplored area of research, there is an urgent need for improved vaccine solutions. The rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and ongoing pan-sarbecovirus vaccine research, have demonstrated the potential of next-generation vaccine platforms and novel antigen design strategies. These advancements offer valuable insights for the development of multistrain PEDV vaccines. This review summarizes key aspects of PEDV virology and explores multistrain vaccine development considering SARS-CoV-2 vaccine innovations, proposing a framework for developing next-generation PEDV vaccine solutions.

Hepatitis B core virus-like particles bearing Pgp3 antigen enhance immune response against genital chlamydial infection in mice.

Chlamydia trachomatis Pgp3 protein-induced immunoprotection is effective but incomplete, which requires the suitable adjuvants to enhance its immune response. Within this context, Hepatitis B core virus-like particles (HBc-VLP) emerge as nanoscale protein particles capable of incorporating either endogenous or exogenous antigens or epitopes. In this study, HBc-Pgp3 chimeric protein was accomplished by integrating the identified dominant epitope of the Pgp3 protein into the major immunodominant region of a truncated HBc-VLP, which was realized in the pET28a (+) vector and expressed via the E. coli BL21 expression system. The efficacious expression and purification of the recombinant HBc-Pgp3 facilitated a tripartite immunization regimen in mice. The immunological assessment encompassed the measurement of IgG antibody and cytokine levels through ELISA, alongside flow cytometric analysis of the CD4+ Th1 cell-mediated immune responses within the murine spleen. Comparative analysis revealed that the HBc-Pgp3-vaccinated mice demonstrated superior IgG antibody titers and subtypes relative to the controls. Moreover, the HBc-Pgp3 formulation was instrumental in augmenting IFN-γ production, enhancing the efficiency of Chlamydia muridarum clearance post-challenge, and severity of hydrosalpinx within the lower genital tract. Collectively, these findings illuminate the potential of the novel HBc-Pgp3 chimeric construct as an innovative vaccine candidate, offering augmented immunoprotection against chlamydial infection.

Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology.

The bacterium responsible for Lyme disease, Borrelia burgdorferi, accumulates high levels of manganese without iron and possesses a polyploid genome, characteristics suggesting potential extreme resistance to radiation. Contrary to expectations, we report that wild-type B. burgdorferi B31 cells are radiosensitive, with a gamma-radiation survival limit for 106 wild-type cells of <1 kGy. Thus, we explored B. burgdorferi radiosensitivity through electron paramagnetic resonance (EPR) spectroscopy by quantitating the fraction of Mn2+ present as antioxidant Mn2+ metabolite complexes (H-Mn). The spirochetes displayed relatively low levels of H-Mn, in stark contrast to the extremely radiation-resistant Deinococcus radiodurans. The H-Mn content as revealed by EPR spectroscopy is sufficiently sensitive to detect small changes in radiosensitivity among B. burgdorferi strains. However, B. burgdorferi cells are significantly more sensitive than predicted by EPR, implicating their linear genome architecture as an additional explanation for radiosensitivity. We then explored the influence of the Mn2+-decapeptide-phosphate antioxidant complex MDP, known to shield proteins during irradiation, and showed that treatment with MDP preserves B. burgdorferi's epitopes at 5 kGy irradiation, which crucially prevents cell proliferation. This finding defines some of the pivotal mechanisms that B. burgdorferi evolved to survive oxidative conditions experienced with tick and mammal immune responses. These observations also provide an opportunity for innovative vaccine development strategies employing ionizing radiation to disrupt the B. burgdorferi genome, while maintaining antigenic potency. These fresh insights extend our understanding of the unique biology of B. burgdorferi and open new avenues for considering novel whole-cell Lyme disease vaccines using MDP and irradiation-based inactivation.IMPORTANCEThe study highlights that electron paramagnetic resonance (EPR) spectroscopy is sufficiently sensitive to detect small differences in radiation resistance among Borrelia burgdorferi strains based on their population of Mn2+-metabolite complexes (H-Mn). B. burgdorferi appears to have evolved a system not to protect from irradiation, but presumably to protect from oxidative stress when cyclically transmitted from tick to mammalian host and back. These data also suggest a path forward in the development of novel vaccines against spirochete infections, including Lyme disease, through preparation involving the synthetic Mn2+-decapeptide-phosphate antioxidant complex MDP to provide B. burgdorferi epitope protection during sterilizing gamma-irradiation that eliminates growth. Given the current lack of effective whole-cell vaccines for Lyme disease, this research identifies a potential strategy for developing alternative radiation-inactivated, yet highly effective vaccines.

The Significance of Vaccines in Mitigating Emerging Infectious Diseases: A Comprehensive Review

Background: The global rise in emerging infectious diseases presents significant challenges to public health, exacerbated by issues such as antimicrobial resistance (AMR). Vaccination remains a pivotal strategy in preventing the spread of these diseases, yet its role is often underappreciated in the context of rising drug resistance. Methods: This review synthesizes current literature on the effectiveness of vaccines and immunotherapeutic approaches in controlling emerging infectious diseases. It analyzes data from clinical studies, epidemiological reports, and the impact of vaccination on AMR trends, particularly in regions severely affected by infectious diseases. Results: Findings indicate that vaccines significantly reduce the incidence and severity of diseases such as tuberculosis, malaria, and COVID-19. Furthermore, immunotherapy, including monoclonal antibodies, demonstrates potential in enhancing host immunity against multidrug-resistant pathogens. Despite advancements, the ongoing rise of AMR, particularly in low- and middle-income countries, poses a considerable threat to the efficacy of existing vaccines and treatments. Conclusion: Vaccination and immunotherapeutic strategies are essential components in the fight against emerging infectious diseases and AMR. Continued investment in vaccine development and implementation is critical to mitigate the impact of these evolving health threats. Future research should focus on innovative vaccine technologies and strategies to enhance public health responses in vulnerable populations.

Development and Evaluation of a Newcastle Disease Virus-like Particle Vaccine Expressing SARS-CoV-2 Spike Protein with Protease-Resistant and Stability-Enhanced Modifications.

The ongoing global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the continuous development of innovative vaccine strategies, especially in light of emerging viral variants that could undermine the effectiveness of existing vaccines. In this study, we developed a recombinant virus-like particle (VLP) vaccine based on the Newcastle Disease Virus (NDV) platform, displaying a stabilized prefusion form of the SARS-CoV-2 spike (S) protein. This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity. Using a prime-boost regimen, we administered NDV-VLP-S-3Q2P intramuscularly at different doses (2, 10, and 20 µg) to BALB/c mice. Robust humoral responses were observed, with high titers of S-protein-specific IgG and neutralizing antibodies against SARS-CoV-2 pseudovirus, reaching titers of 1:2200-1:2560 post-boost. The vaccine also induced balanced Th1/Th2 immune responses, evidenced by significant upregulation of cytokines (IFN-γ, IL-2, and IL-4) and S-protein-specific IgG1 and IgG2a. Furthermore, strong activation of CD4+ and CD8+ T cells in the spleen and lungs confirmed the vaccine's ability to promote cellular immunity. These findings demonstrate that NDV-S3Q2P-VLP is a potent immunogen capable of eliciting robust humoral and cellular immune responses, highlighting its potential as a promising candidate for further clinical development in combating COVID-19.

Challenges of Multidrug-Resistant Tuberculosis Meningitis: Current Treatments and the Role of Glutathione as an Adjunct Therapy.

Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, especially when it involves the central nervous system (CNS). Tuberculous meningitis (TBM), a severe manifestation of TB, is linked to high mortality rates and long-term neurological complications, further exacerbated by drug resistance and immune evasion mechanisms employed by Mycobacterium tuberculosis (Mtb). Although pulmonary TB remains the primary focus of research, MDR-TBM introduces unique challenges in diagnosis, treatment, and patient outcomes. The effectiveness of current treatments is frequently compromised by poor CNS penetration of anti-TB drugs and the necessity for prolonged therapy, which often involves considerable toxicity. This review explores the potential of cytokine-based adjunct immunotherapies for MDR-TBM, addressing the challenges of balancing pro-inflammatory and anti-inflammatory signals within the CNS. A central focus is the prospective role of glutathione, not only in reducing oxidative stress but also in enhancing host immune defenses against Mtb's immune evasion strategies. Furthermore, the development of vaccines aimed at upregulating glutathione synthesis in macrophages represents a promising strategy to bolster the immune response and improve treatment outcomes. By integrating glutathione and innovative vaccine approaches into MDR-TBM management, this review proposes a comprehensive strategy that targets Mtb directly while supporting immune modulation, with the potential to enhance patient outcomes and reduce treatment related adverse effects. We underscore the urgent need for further research into adjunctive therapies and immunomodulatory strategies to more effectively combat MDR-TBM.

Can social media promote vaccination? Strategies and effectiveness of COVID-19 vaccine popularization on Chinese Weibo.

The COVID-19 pandemic has shown a high severity in terms of mortality, and to mitigate the impact of the COVID-19 pandemic, a great deal of reliance has been placed on vaccines with defensive effects. In the context of the transmission of hazardous Omicron variant strains, vaccine popularization and acceptance are very important to ensure world health security. Social media can spread information and increase public confidence in and acceptance of vaccines. In this study, weibos related to "vaccine science popularization" during the COVID-19 pandemic in China were collected, and Weibo publishers were divided into Individuals, Organizations, Media, Government, and Scientists. The communication strategies were analyzed with content analysis from the four dimensions of Issue, Topic, Frame, and Position. SnowNLP was used to mine the audience comments and to assess their emotional tendencies. Finally, hierarchical regression was used to verify the causal relationship between vaccine science popularization strategies and audiences' emotions. We found that the higher the scientific authority of the weibo publisher, the more positive the emotional tendency of the audience toward the weibo. Issues that are scientific, authoritative, and positive topics that positively present the advantages of the COVID-19 vaccine, and frames with detailed narratives, scientific arguments, diversified forms of presentations, and positions in support of the COVID-19 vaccine, positively affect the effect of vaccine popularization. Based on the experience of COVID-19 vaccine promotion in China, the results may serve as a reference for promoting innovative vaccines and handling public health affairs around the world.

Understanding Fish Immunity and Innovative Vaccination Approaches in Aquaculture

Fish possess a unique immune system that, while somewhat similar to mammals, exhibits distinct characteristics. This review paper explains the complexities of fish immunity, highlighting the innate and adaptive immune responses that protect against various pathogens, including bacteria (Aeromonas spp, Flavobacterium columnare, Mycobacterium marinum, Streptococcus iniae, Edwardsiella tarda, Pseudomonas aeruginosa etc), viruses (Infectious Hematopoietic Necrosis Virus (IHNV), Viral Hemorrhagic Septicemia Virus (VHSV) etc.), fungi and parasites (Dioctophyma renale etc). Host-pathogen interactions are dynamic and critical for understanding the immune evasion strategies employed by pathogens, such as antigenic variation, molecular mimicry and biofilm formation. Vaccination is crucial in aquaculture, enhancing fish immunity against diseases through various vaccines, including inactivated, live, subunit, and nucleic acid vaccines. Various delivery methods are employed to maximize immunogenic responses, such as injection, immersion, and oral administration. Additionally, advancements in science and technology have led to innovative techniques to increase vaccine efficacy, including nanoparticle delivery and microencapsulation. Successful vaccination strategies have been adapted to combat significant fish pathogens, demonstrating the potential for enhancing disease resistance in aquaculture. This comprehensive overview underscores the importance of understanding fish immune systems and developing effective vaccination strategies to ensure fish health and sustainability in aquaculture practices.

Vaccine and therapeutic agents against the respiratory syncytial virus: resolved and unresolved issue.

Respiratory syncytial virus (RSV) is a predominant pathogen responsible for respiratory tract infections among infants, the elderly, and immunocompromised individuals. In recent years, significant progress has been made in innovative vaccines and therapeutic agents targeting RSV. Nevertheless, numerous challenges and bottlenecks persist in the prevention and treatment of RSV infections. This review will provide an overview of the resolved and unresolved issues surrounding the development of vaccines and therapeutic agents against RSV. As of September 2024, three RSV vaccines against acute lower respiratory infections (ALRI) have been approved globally. Additionally, there have been notable progress in the realm of passive immunoprophylactic antibodies, with the monoclonal antibody nirsevimab receiving regulatory approval for the prevention of RSV infections in infants. Furthermore, a variety of RSV therapeutic agents are currently under clinical investigation, with the potential to yield breakthrough advancements in the foreseeable future. This review delineates the advancements and challenges faced in vaccines and therapeutic agents targeting RSV. It aims to provide insights that will guide the development of effective preventive and control measures for RSV.

Biotechnological Interventions for the Production of Subunit Vaccines Against Group A Rotavirus.

Group A rotavirus (RVA) is a major cause of severe gastroenteritis in infants and young children globally, despite the availability of live-attenuated vaccines. Challenges such as limited efficacy in low-income regions, safety concerns for immunocompromised individuals, and cold-chain dependency necessitate alternative vaccine strategies. Subunit vaccines, which use specific viral proteins to elicit immunity, provide a safer and more adaptable approach. This review highlights biotechnological advancements in producing subunit vaccines, focusing on recombinant expression systems like bacterial, yeast, insect, mammalian, and plant-based platforms for scalable and cost-effective production of viral proteins. Key innovations include molecular engineering, adjuvant development, and delivery system improvements to enhance vaccine immunogenicity and efficacy. Subunit vaccines and virus-like particles expressed in various systems have demonstrated promising preclinical and clinical results, with some candidates nearing commercial readiness. Reverse vaccinology, combined with Artificial Intelligence and Machine Learning, is driving the development of innovative multiepitope vaccines and antivirals. Strategies such as passive immunization, single-chain antibodies, immunobiotics, and novel antivirals are also explored as alternative management options. The review also underscores advanced genome editing and reverse genetics approaches to improve vaccine design and antiviral therapies. These biotechnological interventions offer hope for equitable and effective control of rotavirus diarrhea, particularly in resource-limited settings, and represent significant progress toward addressing current vaccine limitations.

Vaccine Strategies Against RNA Viruses: Current Advances and Future Directions.

The development of vaccines against RNA viruses has undergone a rapid evolution in recent years, particularly driven by the COVID-19 pandemic. This review examines the key roles that RNA viruses, with their high mutation rates and zoonotic potential, play in fostering vaccine innovation. We also discuss both traditional and modern vaccine platforms and the impact of new technologies, such as artificial intelligence, on optimizing immunization strategies. This review evaluates various vaccine platforms, ranging from traditional approaches (inactivated and live-attenuated vaccines) to modern technologies (subunit vaccines, viral and bacterial vectors, nucleic acid vaccines such as mRNA and DNA, and phage-like particle vaccines). To illustrate these platforms' practical applications, we present case studies of vaccines developed for RNA viruses such as SARS-CoV-2, influenza, Zika, and dengue. Additionally, we assess the role of artificial intelligence in predicting viral mutations and enhancing vaccine design. The case studies underscore the successful application of RNA-based vaccines, particularly in the fight against COVID-19, which has saved millions of lives. Current clinical trials for influenza, Zika, and dengue vaccines continue to show promise, highlighting the growing efficacy and adaptability of these platforms. Furthermore, artificial intelligence is driving improvements in vaccine candidate optimization and providing predictive models for viral evolution, enhancing our ability to respond to future outbreaks. Advances in vaccine technology, such as the success of mRNA vaccines against SARS-CoV-2, highlight the potential of nucleic acid platforms in combating RNA viruses. Ongoing trials for influenza, Zika, and dengue demonstrate platform adaptability, while artificial intelligence enhances vaccine design by predicting viral mutations. Integrating these innovations with the One Health approach, which unites human, animal, and environmental health, is essential for strengthening global preparedness against future RNA virus threats.

MRNA vaccine politics: responsible governance coordination for vaccine innovation in times of urgency

ABSTRACT COVID-19 crisis reaffirmed the power of a few companies to scale up production for mRNA vaccines, which created injustice as a few nations in the developed world benefited first from available vaccines, while LMICs waited at the back of the queue. Initiatives such as the South Africa mRNA tech transfer hub sought to address these concerns. The article engages in an analysis of the different visions that underpin the current vaccine innovation system and the South Africa tech transfer hub. I argue that the dominant vision of global scalability by pharmaceutical companies which are ‘too big to fail’ limits the transformative potential of the hub and I propose ways in which responsible governance coordination can address some of the failings of the system.

Navigating Fish Immunity: Focus on Mucosal Immunity and the Evolving Landscape of Mucosal Vaccines

The growing role of aquaculture in global food security has underscored the need for advanced immunological insights to protect fish health and boost productivity. As aquaculture’s importance rises, understanding fish immunity is crucial for developing effective vaccination strategies. Fish possess a specialized immune system with unique mucosal structures that enable resilience in aquatic environments. This review examines critical advances in fish mucosal immunity, particularly focusing on mucosal vaccines that target infection at primary entry points, such as the gills, skin, and gastrointestinal tract. Mucosal vaccination has demonstrated a compelling capacity to stimulate localized and systemic immune responses, offering enhanced protection against waterborne pathogens. Additionally, this review addresses knowledge gaps from previous research on the global aquaculture vaccines market by offering a regional perspective on industry developments, recent trends, and innovative vaccine formulations. In doing so, it highlights the role of mucosal vaccines in overcoming the specific challenges of fish farming and supporting sustainable aquaculture. This synthesis of current methodologies, industry practices, and future directions contributes to a deeper understanding of fish immunology, ultimately informing strategies to achieve optimal disease management and bolster global aquaculture resilience.