Traditional Vaccines Research Articles

Current Advance and Future of mRNA Vaccine in Cancer Therapy

After years of development, cancer vaccines have gradually become an important part of tumor immunotherapy, and have shown a more rapid development momentum under the background of the current era. The vaccine has the advantages of high efficiency, safety, rapid development potential, cost-effectiveness, etc. In recent years, with the continuous improvement of mRNA technology, relevant technologies in the field of mRNA molecules have also made breakthrough progress, and mRNA vaccines have achieved certain results in cancer treatment. Compared with traditional vaccines, mRNA vaccines can induce the body to produce humoral immunity and cellular immunity at the same time, and the research and development cycle is short, the cost is low, and it can quickly develop candidate vaccines to deal with virus mutation, which is conducive to cancer control. mRNA vaccines have become a current research hotspot and have wide application prospects in the prevention and treatment of tumors and infectious diseases. This article comprehensively discusses the structural characteristics, types, unique advantages and future prospects of mRNA vaccines, in order to help understand the vaccine function and clinical application of mRNA, provide a direction for the development of mRNA drugs, and expect that mRNA cancer vaccines will be used in clinic as soon as possible to benefit patients.

Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.

The group of large clostridial toxins (LCTs) includes toxins A (TcdA) and B (TcdB) from Clostridioides difficile, hemorrhagic and lethal toxins from Paeniclostridium sordellii, alpha toxin from Clostridium novyi (TcnA), and cytotoxin from Clostridium perfringens. These toxins are associated with severe pathologies in livestock, including gas gangrene (P. sordellii and C. novyi), infectious necrotic hepatitis (C. novyi), avian necrotic enteritis (C. perfringens), and enterocolitis (C. difficile). Immunoprophylaxis is crucial for controlling these diseases, but traditional vaccines face production challenges, such as labor-intensive processes, and often exhibit low immunogenicity. This has led to increased interest in recombinant vaccines. While TcdA and TcdB are well-studied for human immunization, other LCTs remain poorly characterized and require further investigation. Therefore, this study emphasizes the importance of understanding lesser-explored toxins and proposes using immunoinformatics to identify their immunodominant regions. By mapping these regions using silico tools and considering their homology with TcdA and TcdB, the study aims to guide future research in veterinary vaccinology. It also explores alternatives to overcome the limitations of conventional and recombinant vaccines, offering guidelines for developing more effective vaccination strategies against severe infections in animals.

Novel dual-pathogen multi-epitope mRNA vaccine development for Brucella melitensis and Mycobacterium tuberculosis in silico approach.

Brucellosis and Tuberculosis, both of which are contagious diseases, have presented significant challenges to global public health security in recent years. Delayed treatment can exacerbate the conditions, jeopardizing patient lives. Currently, no vaccine has been approved to prevent these two diseases simultaneously. In contrast to traditional vaccines, mRNA vaccines offer advantages such as high efficacy, rapid development, and low cost, and their applications are gradually expanding. This study aims to develop multi-epitope mRNA vaccines argeting Brucella melitensis and Mycobacterium tuberculosis H37Rv (L4 strain) utilizing immunoinformatics approaches. The proteins Omp25, Omp31, MPT70, and MPT83 from the specified bacteria were selected to identify the predominant T- and B-cell epitopes for immunological analysis. Following a comprehensive evaluation, a vaccine was developed using helper T lymphocyte epitopes, cytotoxic T lymphocyte epitopes, linear B-cell epitopes, and conformational B-cell epitopes. It has been demonstrated that multi-epitope mRNA vaccines exhibit increased antigenicity, non-allergenicity, solubility, and high stability. The findings from molecular docking and molecular dynamics simulation revealed a robust and enduring binding affinity between multi-epitope peptides mRNA vaccines and TLR4. Ultimately, Subsequently, following the optimization of the nucleotide sequence, the codon adaptation index was calculated to be 1.0, along with an average GC content of 54.01%. This indicates that the multi-epitope mRNA vaccines exhibit potential for efficient expression within the Escherichia coli(E. coli) host. Analysis through immune modeling indicates that following administration of the vaccine, there may be variation in immunecell populations associated with both innate and adaptive immune reactions. These types encompass helper T lymphocytes (HTL), cytotoxic T lymphocytes (CTL), regulatory T lymphocytes, natural killer cells, dendritic cells and various immune cell subsets. In summary, the results suggest that the newly created multi-epitope mRNA vaccine exhibits favorable attributes, offering novel insights and a conceptual foundation for potential progress in vaccine development.

RNA Interference Applied to Crustacean Aquaculture

RNA interference (RNAi) is a powerful tool that can be used to specifically knock-down gene expression using double-stranded RNA (dsRNA) effector molecules. This approach can be used in aquaculture as an investigation instrument and to improve the immune responses against viral pathogens, among other applications. Although this method was first described in shrimp in the mid-2000s, at present, no practical approach has been developed for the use of dsRNA in shrimp farms, as the limiting factor for farm-scale usage in the aquaculture sector is the lack of cost-effective and simple dsRNA synthesis and administration procedures. Despite these limitations, different RNAi-based approaches have been successfully tested at the laboratory level, with a particular focus on shrimp. The use of RNAi technology is particularly attractive for the shrimp industry because crustaceans do not have an adaptive immune system, making traditional vaccination methods unfeasible. This review summarizes recent studies and the state-of-the-art on the mechanism of action, design, use, and administration methods of dsRNA, as applied to shrimp. In addition, potential constraints that may hinder the deployment of RNAi-based methods in the crustacean aquaculture sector are considered.

Recent Advances in Designing Adeno-Associated Virus-Based Vaccines Against Viral Infections

Over 80% of the world’s deadliest pandemics are caused by viral infections, and vaccination remains the most effective way to prevent these infections from spreading. Since the discovery of the first vaccine over two centuries ago, several vaccine design technologies have been developed. Next-generation vaccines, based on mRNA and viral vector technologies, have recently emerged as alternatives to traditional vaccines. Adenoviral vector-based vaccines against coronavirus disease 2019 have demonstrated a more sustained antibody response as compared to mRNA vaccines. However, this has not been without complications, with a few cases of severe adverse events identified in vaccinated individuals, and the underlying mechanism is the subject of intense investigation. Adeno-associated viral vectors induce a weaker cellular immune response compared to adenoviral vectors, and it is mainly for this reason that there has been a diminished interest in exploring them as a vaccine platform until recently. This review will discuss recent developments and the potential of adeno-associated viral vectors as anti-viral vaccines.

Revolutionizing Influenza Treatment: A Deep Dive into Targeted Drug Delivery Systems.

Influenza, a highly transmissible respiratory infection caused by influenza viruses A and B, poses a persistent threat to global public health due to its high mutation rate, ability to develop resistance to existing antiviral drugs, and capacity for rapid spread. Current treatment options, including four main classes of antiviral agents-adamantanes, neuraminidase inhibitors, RNA-dependent RNA polymerase inhibitors, and polymerase acidic endonuclease inhibitors- are limited by the emergence of drug-resistant viral strains, non-specific drug distribution, and adverse side effects. Moreover, the effectiveness of traditional vaccines is often compromised by antigenic drift and shift, necessitating the development of alternative therapeutic strategies. This review comprehensively explores the potential of novel targeted drug delivery systems to address these limitations and improve influenza management. Nanotechnology-based platforms, including lipid-based, polymer-based, inorganic, and hybrid nanoparticles, offer enhanced drug delivery through improved bioavailability, targeted action, and controlled release, thus minimizing systemic toxicity and optimizing therapeutic outcomes. Inhalation delivery systems such as dry powder inhalers (DPIs), nebulizers, and nanotechnology-based inhalation formulations provide direct delivery of antiviral agents to the respiratory tract, ensuring rapid onset of action with reduced systemic side effects. Transdermal delivery methods, including microneedle patches and hydrogel-based systems, offer non-invasive alternatives that enhance patient compliance and allow for sustained drug release. Furthermore, this review discusses recent innovations, such as responsive drug delivery systems and multifunctional nanoparticles capable of simultaneous delivery of multiple therapeutic agents, representing a significant advancement in the fight against influenza. These novel approaches promise improved targeting and efficacy and enable personalized treatment strategies, enhancing patient outcomes in both seasonal flu and pandemic scenarios. Integrating these advanced drug delivery systems into clinical practice could revolutionize the management of influenza, offering a promising pathway toward more effective and safer therapies.

A mathematical model simulating the adaptive immune response in various vaccines and vaccination strategies

Vaccination has been widely recognized as an effective measure for preventing infectious diseases. To facilitate quantitative research into the activation of adaptive immune responses in the human body by vaccines, it is important to develop an appropriate mathematical model, which can provide valuable guidance for vaccine development. In this study, we constructed a novel mathematical model to simulate the dynamics of antibody levels following vaccination, based on principles from immunology. Our model offers a concise and accurate representation of the kinetics of antibody response. We conducted a comparative analysis of antibody dynamics within the body after administering several common vaccines, including traditional inactivated vaccines, mRNA vaccines, and future attenuated vaccines based on defective interfering viral particles (DVG). Our findings suggest that booster shots play a crucial role in enhancing Immunoglobulin G (IgG) antibody levels, and we provide a detailed discussion on the advantages and disadvantages of different vaccine types. From a mathematical standpoint, our model proposes four essential approaches to guide vaccine design: enhancing antigenic T-cell immunogenicity, directing the production of high-affinity antibodies, reducing the rate of IgG decay, and lowering the peak level of vaccine antigen-antibody complexes. Our study contributes to the understanding of vaccine design and its application by explaining various phenomena and providing guidance in comprehending the interactions between antibodies and antigens during the immune process.

Recent approaches in clinical trials of hepatitis C virus vaccine, challenges and future directions

Globally HCV infects more than 170 million individuals and is a major risk of hepatocellular carcinoma, liver cirrhosis and transplantation. Recent antiviral therapy has significant side effects and is much expensive. During the early infection with HCV, the asymptomatic characteristics have a remarkable impact which results in unknowingly spreading HCV. Recently there is no effective vaccine available. Data indicate that a considerable proportion of individuals naturally manages HCV infection through immune feedback mechanisms, suggesting that developing an effective vaccine against HCV presents a reasonable challenge. Therefore, to control this deadly virus a prophylactic vaccine is compulsory. Different types of methods are adapted to design an effective HCV vaccine which are under different human clinical trials. The current review discusses the goals of the HCV vaccine, traditional vaccine methods, vaccine approaches and challenges in the development of vaccine design.

Prospects of universal influenza virus vaccine and the current challenges of new antiviral drugs

The profound impact of influenza viruses on human health persists as a significant burden, given their potent capacity to cause morbidity and mortality. Despite efforts to mitigate the annual burden of influenza, the effectiveness of current seasonal vaccines in providing substantial protection falls short, leaving undesirable pandemic of influenza viruses. The challenges posed by the influenza pandemic lies from the constant changes inherent in the virus itself, as well as the limitations of current immunization approaches in achieving sufficient immunogenicity. Influenza viruses exhibit antigenic drift and shift, undergoing antigenic evolution by altering the surface glycoproteins. These changes contribute to the persistent and dynamic nature of the influenza virus, posing formidable challenges to effective prevention and control strategies. Currently, there is growing recognition of unique viral targets that hold promise development of broad-protective vaccines against influenza. These targets are distinct from traditional vaccine targets and offer the potential for more comprehension protection against diverse strains of the virus. Here, we present a review about the novel drugs and vaccines that target the influenza virus would signify the unique immune correlates of protection that need to be initiated to accelerate the vaccine efficacy.

Self-Assembling Peptides for Vaccine Adjuvant Discovery

Vaccination is credited as a significant medical achievement contributing to the decline in morbidity and mortality of infectious diseases. Traditional vaccines composed of inactivated and live-attenuated whole pathogens confer the induction of potent and long-term immune responses; however, traditional vaccines pose a high risk of eliciting autoimmune and allergic responses as well as inflammations. New modern vaccines, such as subunit vaccines, employ minimum pathogenic components (such as carbohydrates, proteins, or peptides), overcome the drawbacks of traditional vaccines and stimulate effective immunity against infections. However, the low immunogenicity of subunit vaccines requires effective immune stimulants (adjuvants), which are an indispensable factor in vaccine development. Although there are several approved adjuvants in human vaccines, the challenges of matching and designing appropriate adjuvants for specific vaccines, along with managing the side effects and toxicity of existing adjuvants in humans, are driving the development of new adjuvants. Self-assembling peptides are a promising biomaterial rapidly emerging in the fields of biomedicine, vaccination and material science. Here, peptides self-assemble into ordered supramolecular structures, forming different building blocks in nanoparticle size, including fibrils, tapes, nanotubes, micelles, hydrogels or nanocages, with great biostability, biocompatibility, low toxicity and effectiveness at controlled release. Self-assembling peptides are effective immunostimulatory agents used in vaccine development to enhance and prolong immune responses. This review describes the predominant structures of self-assembling peptides and summarises their recent applications as vaccine adjuvants. Challenges and future perspectives on self-assembled peptides as vaccine adjuvants are also highlighted.

Beyond traditional vaccines: Semi-purified low-pathogenic avian influenza H9N2 virus-like particles and their promise for broiler immunity

Background and Aim: Avian influenza is a global threat to avian species, particularly in developing countries. Recombinant vaccines, including virus-like particles (VLPs), are promising strategies for preventing the spread of the disease. VLPs produced through the self-assembly of viral structural proteins without genomic material mimic native virions and are promising platforms for new vaccines. VLPs have been shown to elicit protective antibodies and are effective and safe vaccines against influenza. This study aimed to optimize the protocol for the production and characterization of H9N2 VLPs and their evaluation as a vaccine in broiler birds. Materials and Methods: Low-pathogenic influenza virus (LPAI) H9N2 was isolated and characterized through whole-genome sequencing, and a VLP-based vaccine for LPAI H9N2 was prepared using a baculovirus expression system. Codon-optimized hemagglutinin (HA), neuraminidase (NA), and M1 were successfully cloned in pFastbac1 and expressed in SF9 cells. Proteins were characterized using sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and electron microscopy after purification. Semi-purified proteins were tested as a vaccine in broiler chickens challenged with LPAI H9N2. Results: Recombinant Bacmid DNA from positive clones was extracted and confirmed using a polymerase chain reaction. The transfection showed cytopathic effects, and the proteins were confirmed through western blotting and SDS-PAGE, which showed the sizes of HA = 62–64 KD, NA = 52 KD, and M1 = 25 KD. The shape and morphology were confirmed through transmission electron microscopy which revealed 100–150 nm size particles. As a result, the semi-purified VLPs (HA assay: 256) were tested as a vaccine for specific-pathogen free broiler birds; administered through subcutaneous and intranasal routes. The birds were challenged on the 28th day after vaccination with the H9N2 strain, and the birds showed significant cross-reactivity with the H9N2 strain. Conclusion: The semi-purified VLP-based vaccine induced a significant immune response in vivo. This vaccine formulation has the potential to control avian influenza outbreaks in Pakistan’s poultry industry. Keywords: avian influenza virus, baculovirus expression system, H9N2, recombinant vaccine, virus-like particles.

A new multi-epitope DNA vaccine against Helicobacter Pylori infection in a BALB/c mouse model

BackgroundHelicobacter Pylori (H. Pylori) is a pathogen that may invade the human stomach. This bacterial strain is now causing widespread concern and considerable health issues worldwide. In contrast to antibiotic treatment, which may lead to drug resistance, vaccination therapy is emerging as a possible immunotherapy option for H. Pylori. DNA vaccines are a potential option to traditional vaccines among vaccine research methods. Furthermore, the multiepitope DNA vaccination may induce a broader immune response to suppress H. Pylori infection. MethodsFour target antigenic proteins (outer membrane beta-barrel, outer membrane beta, HofA, and hcp beta-lactamase-like protein) were used to identify epitopes. The best B and T cell epitopes were selected to induce humoral and cellular immune responses and were connected using the HEYGAEALERAG and GGGS linkers. The peptide's physicochemical characteristics, secondary and tertiary structures, antigenicity, and allergenicity were evaluated utilizing several bioinformatics tools. The multiepitope peptide was successfully inserted into the pcDNA3.1 expression vector. The immunological responses of both the vaccinated and control groups were evaluated by measuring cytokines and antibodies. ResultsBased on the data, the multiepitope peptide consists of 278 amino acid residues and has an average molecular weight (MW) of 28643.61 Da. The peptide residues were mainly situated within the preferred and permitted areas of the Ramachandran plot, accounting for 92.86% of the total. The VaxiJen server has calculated that the multiepitope peptide has an antigenicity score of 1.0067. BALB/c mice vaccinated with the DNA vaccine produced significantly higher levels of specific IgG antibodies (p<0.05). The vaccinated mice exhibited a TH1-type cellular immune response characterized by the generation of IFN-γ and a longer length of life compared to the control animals (p<0.05). In addition, the vaccination group exhibited a substantial increase in the expression level of IFN-γ and IL-1β genes compared to the control group (p<0.05). ConclusionsThe results demonstrated that the multiepitope DNA vaccine elicited significant humoral and cellular responses, and increased survival time in BALB/c mice, indicating that selecting potential epitopes may be a viable technique for developing multiepitope-based vaccines. This can help to introduce effective vaccines.

The Potential of mRNA Vaccines to Fight Against Viruses.

Vaccines have always been a critical tool in preventing infectious diseases. However, the development of traditional vaccines often takes a long time and may struggle to address the challenge of rapidly mutating viruses. The emergence of mRNA technology has brought revolutionary changes to vaccine development, particularly in rapidly responding to the threat of emerging viruses. The global promotion of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 has demonstrated the importance of mRNA technology. Also, mRNA vaccines targeting viruses such as influenza, respiratory syncytial virus, and Ebola are under development. These vaccines have shown promising preventive effects and safety profiles in clinical trials, although the duration of immune protection is still under evaluation. However, the development of mRNA vaccines also faces many challenges, such as stability, efficacy, and individual differences in immune response. Researchers adopt various strategies to address these challenges. Anyway, mRNA vaccines have shown enormous potential in combating viral diseases. With further development and technological maturity, mRNA vaccines are expected to have a profound impact on public health and vaccine equity. This review discussed the potential of mRNA vaccines to fight against viruses, current progress in clinical trials, challenges faced, and future prospects, providing a comprehensive scientific basis and reference for future research.

Plant-based vaccines against viral hepatitis: A panoptic review.

The traditional vaccines against hepatitis have been instrumental in reducing the incidence of some types of viral hepatitis; however, the need for cost-effective, easily distributable, and needle-free vaccine alternatives has led to the exploration of plant-based vaccines. Plant-based techniques offer a promising avenue for producing viral hepatitis vaccines due to their low-cost cultivation, scalability, and the potential for oral administration. This review highlights the successful expression of hepatitis B surface antigens in plants and the subsequent formation of virus-like particles, which have shown immunogenicity in preclinical and clinical trials. The challenges such as achieving sufficient antigen expression levels, ensuring consistent dosing, and navigating regulatory frameworks, are addressed. The review considers the potential of plant-based vaccines to meet the demands of rapid vaccine deployment in response to outbreaks and their role in global immunization strategies, particularly in resource-limited settings. This review underscores the significant strides made in plant molecular farming and the potential of plant-based vaccines to complement existing immunization methods against viral hepatitis.

Development of a recombinant Lactobacillus plantarum oral vaccine expressing VP2 protein for preventing feline panleukopenia virus

Feline panleukopenia virus (FPV) represents a significant health threat to the kittens. While traditional vaccines administered via subcutaneous or intramuscular injection are effective, they can induce stress and adverse reactions. Moreover, unvaccinated kittens visiting veterinary clinics risk exposure to FPV, increasing their susceptibility to infection. Therefore, there is an urgent need for a safer, more gentle vaccination method with streamlined administration. In this study, we developed a recombinant L. plantarum NC8/VP2 expressing the VP2 protein of the prevalent Chinese FPV strain, FPV-251. Our results show that L. plantarum NC8/VP2 effectively colonizes the feline intestinal tract and induces high levels of neutralizing antibodies through oral administration. Kittens exhibited significant protection against FPV-251 infection and associated illnesses or fatalities after 30 days of continuous dosing. These results highlight the potential of recombinant L. plantarum NC8/VP2 as a novel oral vaccine for FPV, presenting a promising approach for disease prevention in domestic cats.

Virus-like particles in poultry disease: an approach to effective and safe vaccination.

The poultry industry, a cornerstone of global food security, faces dynamic challenges exacerbated by viral diseases. This review traces the trajectory of poultry vaccination, evolving from traditional methods to the forefront of innovation Virus-Like Particle (VLP) vaccines. Vaccination has been pivotal in disease control, but traditional vaccines exhibit some limitations. This review examines the emergence of VLPs as a game-changer in poultry vaccination. VLPs, mimicking viruses without replication, offer a safer, targeted alternative with enhanced immunogenicity. The narrative encompasses VLP design principles, production methods, immunogenicity, and efficacy against major poultry viruses. Challenges and prospects are explored, presenting VLP vaccines as a transformative technique in poultry disease control. Understanding their potential empowers industry stakeholders to navigate poultry health management with precision, promising improved welfare, reduced economic losses, and heightened food safety.

Trust in government, social media and willingness to vaccinate

Vaccine hesitancy is considered one of the biggest global health threats. The prevalence of false information about vaccines on social media amplifies this challenge, making it more urgent. This study examines the relationship between social media use, trust in information sources, beliefs about vaccination rates, and willingness to adopt vaccines using data gathered in late 2023 from 975 respondents in South Africa. Our results suggest that people who rely on social media as their primary news source are more hesitant to get vaccinated for themselves and their children. Trust, which includes various sources including confidence in the government, is positively linked to vaccination decisions. Trust is especially important when it comes to less traditional vaccines such as COVID-19 and flu vaccines for both adults and children. We also note gender differences, with South African men showing more reluctance to get vaccinated as adults. Additionally, there is a negative correlation between social media use and the willingness of males to get vaccinated, but this relationship is not evident among females. Our research highlights the need for targeted interventions aimed at improving vaccine uptake, taking into account the links with information sources about vaccination and government trust.

Mpox treatment evolution: past milestones, present advances, and future directions.

An underestimated worldwide health concern, Monkeypox (Mpox) is becoming a bigger menace to the world's population. After smallpox was eradicated in 1970, Mpox was found in a rural region of Africa and quickly spread to other African countries. The etiological agent of the Mpox infection, the Mpox virus, is constantly evolving, and its capability for cross-species transmission led to a global outbreak in 2022 which led to several deaths throughout the world. This review aims to showcase the progressive treatment methods and emerging innovations in the diagnostic and prevention strategies for controlling Mpox. The clinical trial data for antiviral drugs were systematically collected and analyzed using statistical tests to determine the most effective antiviral treatment. Emerging viral protein inhibitors that are under investigation for Mpox treatment were also scrutinized in this review. Additionally, modern diagnostic methods, such as the Streamlined CRISPR On Pod Evaluation platform (SCOPE) and graphene quantum rods were reviewed, and the efficacy of mRNA vaccines with traditional smallpox vaccines used for Mpox were compared. The statistical analysis revealed that tecovirimat (TCV) is the most effective antiviral drug among the other evaluated drugs, showing superior efficacy in clinical trials. Similarly, mRNA vaccines offer greater effectiveness compared to conventional smallpox vaccines. Furthermore, emerging nanomedicine and herbal drug candidates were highlighted as potential future treatments for Mpox. The findings underscore the effectiveness of TCV in treating Mpox and highlight significant advancements in preventive treatments. The review also points to innovative approaches in vaccine technology and potential future therapies, including nanomedicine and herbal remedies, which may enhance Mpox management.

Harnessing the potential of the NALT and BALT as targets for immunomodulation using engineering strategies to enhance mucosal uptake.

Mucosal barrier tissues and their mucosal associated lymphoid tissues (MALT) are attractive targets for vaccines and immunotherapies due to their roles in both priming and regulating adaptive immune responses. The upper and lower respiratory mucosae, in particular, possess unique properties: a vast surface area responsible for frontline protection against inhaled pathogens but also simultaneous tight regulation of homeostasis against a continuous backdrop of non-pathogenic antigen exposure. Within the upper and lower respiratory tract, the nasal and bronchial associated lymphoid tissues (NALT and BALT, respectively) are key sites where antigen-specific immune responses are orchestrated against inhaled antigens, serving as critical training grounds for adaptive immunity. Many infectious diseases are transmitted via respiratory mucosal sites, highlighting the need for vaccines that can activate resident frontline immune protection in these tissues to block infection. While traditional parenteral vaccines that are injected tend to elicit weak immunity in mucosal tissues, mucosal vaccines (i.e., that are administered intranasally) are capable of eliciting both systemic and mucosal immunity in tandem by initiating immune responses in the MALT. In contrast, administering antigen to mucosal tissues in the absence of adjuvant or costimulatory signals can instead induce antigen-specific tolerance by exploiting regulatory mechanisms inherent to MALT, holding potential for mucosal immunotherapies to treat autoimmunity. Yet despite being well motivated by mucosal biology, development of both mucosal subunit vaccines and immunotherapies has historically been plagued by poor drug delivery across mucosal barriers, resulting in weak efficacy, short-lived responses, and to-date a lack of clinical translation. Development of engineering strategies that can overcome barriers to mucosal delivery are thus critical for translation of mucosal subunit vaccines and immunotherapies. This review covers engineering strategies to enhance mucosal uptake via active targeting and passive transport mechanisms, with a parallel focus on mechanisms of immune activation and regulation in the respiratory mucosa. By combining engineering strategies for enhanced mucosal delivery with a better understanding of immune mechanisms in the NALT and BALT, we hope to illustrate the potential of these mucosal sites as targets for immunomodulation.

Clinical trials and recent progress in HIV vaccine development.

The greatest obstacle for scientists is to develop an effective HIV vaccine. An effective vaccine represents the last hope for halting the unstoppable global spread of HIV and its catastrophic clinical consequences. Creating this vaccine has been challenging due to the virus's extensive genetic variability and the unique role of cytotoxic T lymphocytes (CTL) in containing it. Innovative methods to stimulate CTL have demonstrated significant therapeutic advantages in nonhuman primate model systems, unlike traditional vaccination techniques that are not expected to provide safe and efficient protection against HIV. Human clinical trials are currently evaluating these vaccination strategies, which involve plasmid DNA and live recombinant vectors. This review article covers the existing vaccines and ongoing trial vaccines. It also explores the different approaches used in developing HIV vaccines, including their molecular mechanisms, target site effectiveness, and potential side effects.