Vaccine Approaches Research Articles

Immune Responses to Respiratory Syncytial Virus Vaccines: Advances and Challenges

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory infections, particularly in children and the elderly. This virus primarily infects ciliated epithelial cells and activates alveolar macrophages and dendritic cells, triggering an innate antiviral response that releases pro-inflammatory cytokines. However, immunity generated by infection is limited, often leading to reinfection throughout life. This review focuses on the immune response elicited by newly developed and approved vaccines against RSV. A comprehensive search of clinical studies on RSV vaccine candidates conducted between 2013 and 2024 was performed. There are three primary target groups for RSV vaccines: pediatric populations, infants through maternal immunization, and the elderly. Different vaccine approaches address these groups, including subunit, live attenuated or chimeric, vector-based, and mRNA vaccines. To date, subunit RSV vaccines and the mRNA vaccine have been approved using the pre-fusion conformation of the F protein, which has been shown to induce strong immune responses. Nevertheless, several other vaccine candidates face challenges, such as modest increases in antibody production, highlighting the need for further research. Despite the success of the approved vaccines for adults older than 60 years and pregnant women, there remains a critical need for vaccines that can protect children older than six months, who are still highly vulnerable to RSV infections.

EXTH-15. AN EGFRVIII RNA-LNP VACCINE PROTOTYPE ACHIEVES TUMOUR CLEARANCE IN A GBM MOUSE MODEL

Abstract Glioblastoma (GBM) is an aggressive high-grade glioma that is fatal despite standard-of-care therapy. Recurrent somatic alterations that form neoantigens represent opportunities for targeted therapeutic intervention. Using human EGFRvIII as a prototypical structural alteration and neoantigen, we tested the potential of a mRNA-LNP vaccine approach to improve the survival of mice with EGFRvIII-driven GBM. To generate the model, we used in vivo electroporation to introduce genetic alterations (EGFRvIII-OE/CDKN2A-KO/PTEN-KO) into periventricular cells of early postnatal C3H mice, then propagated cells from the subsequent tumours to create implantable cell lines. Following orthotopic implantation, the resulting syngeneic tumours faithfully recapitulate histologic features of GBM with infiltrative growth, mitoses, necrosis, and vascular proliferation. Also like human GBM, the models are sensitive to but not cured by temozolomide chemotherapy and are resistant to immune checkpoint blockade. We delivered mRNA-LNP vaccines against EGFRvIII into the thigh muscle of tumour-bearing mice on days 7, 10, 14, 21, and 36 after tumour cell implant. We observed no tumour in vaccine-treated mice compared to significant tumour burden in control vector-treated animals by MR imaging at day 30 post-tumour cell implant. By day 37, all control-treated mice had died, whereas vaccine-treated mice cleared their tumours with no tumour burden detectable by histology at day 150 (N= 5 per group, **p= 0.0023). In a follow-up experiment with vaccine or control treatment on days 10, 14, 18, and 25 post-cell implants, all control mice had died by day 39. Further, vaccine-treated surviving animals were re-challenged with tumour cell implant into the contralateral hemisphere on day 42 and remain alive as of day 90. Our ongoing proof-of-principle work demonstrates that neoantigen driver mutations in high-grade glioma models can be targeted with an mRNA lipid vaccine. We hope this pre-clinical work will lead to early-phase clinical trials.

Exogenous or in situ vaccination to trigger clinical responses in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease for which remarkable therapeutic resistance is the norm. Conventional immunotherapies, like immune checkpoint inhibitors, show limited efficacy in PDA due to a remarkably immunosuppressive tumor microenvironment (TME) and systemic inflammation. This review discusses the potential of both exogenous and in situ vaccination strategies to overcome these barriers and enhance anti-tumor immunity in PDA. Exogenous vaccines, including whole-cell, dendritic cell, peptide, and nucleic acid-based vaccines, have shown varying degrees of promise but face challenges related to antigen selection, production complexities, and patient-specific factors. In contrast, in situ vaccination strategies leverage conventional cytotoxic therapies, such as chemotherapy and radiation therapy, to induce immunogenic cell death and modulate the TME with the aim to stimulate anti-tumor immunity. While preclinical studies support the use of in situ vaccination, balancing the stimulatory and inhibitory effects is likely fundamental to eliciting productive anti-tumor responses in patients. Ongoing research seeks to identify new innovative strategies that can harness the endogenous immune response and trigger in situ vaccination. Overall, while both vaccination approaches offer significant potential, further research and clinical trials will be needed to optimize these strategies for improving patient outcomes in PDA.

Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions

After the COVID-19 pandemic, mRNA-based vaccines have emerged as a revolutionary technology in immunization and vaccination. These vaccines have shown remarkable efficacy against the virus and opened up avenues for their possible application in other diseases. This has renewed interest and investment in mRNA vaccine research and development, attracting the scientific community to explore all its other applications beyond infectious diseases. Recently, researchers have focused on the possibility of adapting this vaccination approach to cancer immunotherapy. While there is a huge potential, challenges still remain in the design and optimization of the synthetic mRNA molecules and the lipid nanoparticle delivery system required to ensure the adequate elicitation of the immune response and the successful eradication of tumors. This review points out the basic mechanisms of mRNA-LNP vaccines in cancer immunotherapy and recent approaches in mRNA vaccine design. This review displays the current mRNA modifications and lipid nanoparticle components and how these factors affect vaccine efficacy. Furthermore, this review discusses the future directions and clinical applications of mRNA-LNP vaccines in cancer treatment.

Specific anti-toxic immunotherapy: use in medical practice and perspectives

The results of use of approaches and means of antitoxic immunotherapy in medical practice are summarized: passive transfer of various variants of antibodies specific to toxic compounds, vaccination – specific active immunization with vaccines carrying determinants of the immunochemical specificity of target toxic compounds. The practical effectiveness of the known approaches of passive transfer and vaccination is associated with the ability of specific antibodies, by binding target bioactive compounds with pronounced toxicity, to change the availability of corresponding structures in the body-targets and, in the presence of a sufficient number of specific antibodies with high binding ability to the target compounds, neutralize their toxicity. In medical practice, polyspecific heterologous antisera or the gamma globulin fraction of antisera (extremely rare monoclonal antibodies of narrow specificity) are widely used for passive transfer as antidotes in the treatment of victims in order to prevent deaths and extensive necrosis of soft tissues at the site of the bite of poisonous snakes and insects. Active immunization – vaccination with appropriate antigenic drugs should create in immunized individuals a state of humoral immunity with the corresponding characteristics of antibody formation specific to the target compound. When a target toxic compound enters an immunized organism, it is also possible to neutralize its toxicity. The most successful experience in using the principles of active immunization as a technology for specific antitoxic therapy is associated with the practice of using toxoids for toxinemic infections. Specific practical techniques used to achieve the effectiveness of possible approaches to specific antitoxic immunotherapy in the form of passive transfer of specific antibodies or their fragments are considered: to combat lethal infections in the pathogenesis of which the toxic effects of bacterial exotoxins are significant; when treating victims of snake and insect bites, exposure to poisons of marine organisms, algae and plant toxins; in the treatment of severe intoxication with certain low molecular weight toxic substances: digoxin, colchicine, tricyclic antidepressants. The most successful experiences of using the principles of active immunization as a technology for specific antitoxic therapy, based on the use of toxoids with specificity for diphtheria, tetanus, botulism, cholera, typhoid fever, dysentery, gas gangrene and other toxinemic infections, are also considered. The fairly high immunogenicity of toxoids with the possibility of activating both constitutional and adaptive immunity has become the basis for their use as macromolecular carriers of hapten analogues of narcotic substances – a promising direction in drug addiction, in the implementation of which a number of experimental molecular and combined vaccines of opiates, methamphetamine, cocaine, and nicotine. This variant of practical efforts in medicine can be regarded as a new direction of specific antitoxic immunotherapy – an option to combat drug addiction by vaccinating drug addicts.

Headless hemagglutinin-containing influenza viral particles direct immune responses toward more conserved epitopes.

Seasonal influenza vaccines provide mostly strain-specific protection due to the elicitation of antibody responses focused on evolutionarily plastic antigenic sites in the hemagglutinin head domain. To direct the humoral response toward more conserved epitopes, we generated an influenza virus particle where the full-length hemagglutinin protein was replaced with a membrane-anchored, "headless" variant while retaining the normal complement of other viral structural proteins such as the neuraminidase as well as viral RNAs. We found that a single administration of a headless virus particle-based vaccine elicited high titers of antibodies that recognized more conserved epitopes on the major viral glycoproteins. Furthermore, the vaccine could elicit these responses even in the presence of pre-existing, hemagglutinin (HA) head-focused influenza immunity. Importantly, these antibody responses mediated protective, but non-neutralizing functions such as neuraminidase inhibition and antibody-dependent cellular cytotoxicity. Additionally, we show the vaccine can provide protection from homologous and heterologous challenges in mouse models of severe influenza without any measurable HA head-directed antibody responses. Thus, headless hemagglutinin containing viral particles may represent a tool to drive the types of antibody responses predicted to increase influenza vaccine breadth and durability.IMPORTANCECurrent seasonal influenza vaccines provide incomplete protection from disease. This is partially the result of the antibody response being directed toward parts of the virus that are tolerant of mutations. Redirecting the immune response to more conserved regions of the virus has been a central strategy of next-generation vaccine designs and approaches. Here, we develop and test a vaccine based on a modified influenza virus particle that expresses a partially deleted hemagglutinin protein along with the other viral structural proteins. We demonstrate this vaccine elicits antibodies that recognize the more conserved viral epitopes of the hemagglutinin stalk and neuraminidase protein to facilitate protection against influenza viruses despite a lack of classical viral neutralization activity.

Provider and community perceptions of integrated COVID-19 and routine childhood immunisation programmes in Nigeria: a qualitative exploratory study

BackgroundIn Nigeria, COVID-19 vaccines were delivered through outreach activities, as well as integrated within routine immunisation. However, evaluations of integrated approaches for novel vaccines are scarce. We aimed to understand the perceived benefits and challenges of integrating the COVID-19 vaccine within routine immunisation in Nigeria, and identify ways to strengthen this approach.MethodsWe conducted 30 semi-structured interviews with community members and healthcare workers in primary healthcare facilities (PHCs) in Jigawa (n = 16) and Oyo (n = 14) states, Nigeria from 08 August to 13 September 2022. Participants were selected purposively from PHCs. We obtained information on participants’ perception about routine immunisation, and perceived benefits and challenges associated with integrated COVID-19 vaccine delivery. Healthcare worker and community interviews were analysed separately following a thematic analysis approach.ResultsWe identified four themes that describe the community and healthcare workers’ responses, perceived impact, and the health system adaptions to the challenges associated with the integrated vaccine delivery approach. Community members expressed concern that children might be given COVID-19 vaccines instead of routine immunisations, while others appreciated the integrated approach due to their trust in the efficacy of COVID-19 vaccines, government, and healthcare providers. Healthcare providers perceived the integrated approach as improving vaccination coverage and awareness but noted additional problems of increased workload, vaccine scarcity, and prolonged clinic visits. Insufficient resources were subsisting barriers to effective integration in both states, but the provider’s gender was also a challenge in Jigawa state. Additionally, the use of incentives to generate demand had ambiguous effects in Jigawa state.ConclusionTaking an integrated approach to deliver COVID-19 vaccines was acceptable by healthcare providers but community members expressed concerns. Given existing vaccination programmes have persistent challenges, it is pertinent to address these barriers to enhance effectiveness of an integrated approach.

Research Progress of Immune Mechanisms Related to Persistent HPV Infection in CIN after Cervical Conization

Persistent human papillomavirus (HPV) infection is associated with the grading of cervicalintraepithelial neoplasia (CIN), high-risk HPV infection, multiple HPV infections, high HPV load,HPV infection of surgical margin, and age in CIN after conization. The immune mechanism iscomplex and is primarily related to vaginal microecology disorders, immune escape, immuneresponse impairment, and the release of regulatory cytokines. Currently, the treatment methods forpostoperative persistent HPV infection include surgical treatment, antiviral treatment, vaccination,and other approaches.

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.

Meeting Report: Controlled Human Influenza Virus Infection Model Studies: Current Status and Future Directions for Innovation.

On November 13-14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de-risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.

Modelling vaccination approaches for mpox containment and mitigation in the Democratic Republic of the Congo.

Mpox was first identified in the Democratic Republic of the Congo (DRC) in 1970. In 2023, a historic outbreak of mpox occurred in the country, continuing into 2024. Over 14 000 cases and 600 deaths were reported in 2023 alone, representing a major increase from previous outbreaks. The modified vaccinia Ankara vaccine (brand names JYNNEOS, Imvamune, and Imvanex) was used in the 2022 mpox outbreak in the USA and Europe. However, at the time of the study, vaccination had not been made available in the DRC. We aimed to inform policy and decision makers on the potential benefits of, and resources needed, for mpox vaccination campaigns in the DRC by providing counterfactual scenarios evaluating the short-term effects of various vaccination strategies on mpox cases and deaths, if such a vaccination campaign had been undertaken before the 2023-24 outbreak. A dynamic transmission model was used to simulate mpox transmission in the DRC, stratified by age (<5, 5-15, and >15 years) and province. The model was used to simulate potential vaccination strategies, varying by age and region (endemic provinces, non-endemic provinces with historic cases, and all provinces) assessing the effect the strategies would have on deaths and cases in an epidemic year similar to 2023. In addition, we estimated the number of vaccine doses needed to implement each strategy. Without vaccination, our model predicted 14 700 cases and 700 deaths from mpox over 365 days. Vaccinating 80% of all children younger than 5 years in endemic regions led to a 27% overall reduction in cases and a 43% reduction in deaths, requiring 10·5 million vaccine doses. Vaccinating 80% of all children younger than 5 years in all regions led to a 29% reduction in cases and a 43% reduction in deaths, requiring 33·1 million doses. Vaccinating 80% of children aged 15 years or younger in endemic provinces led to a 54% reduction in cases and a 71% reduction in deaths, requiring 26·6 million doses. When resources are limited, vaccinating children aged 15 years or younger, or younger than 5 years, in endemic regions of the DRC would be the most efficient use of vaccines. Further research is needed to explore long-term effects of a one-time or recurrent vaccination campaign. Canadian Institutes of Health Research, Canadian International Development Research Centre, US Department of Defense (Defense Threat Reduction Agency, Mpox Threat Reduction Network), Global Affairs Canada (Weapons Threat Reduction Program), US Department for Agriculture (Agriculture Research Service, Non-Assistance Cooperative Agreement).

A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis.

Memory T cells play a key role in immune protection against cancer. Vaccine-induced tissue-resident memory T (TRM) cells in the lung have been shown to protect against lung metastasis. Identifying the source of lung TRM cells can help to improve strategies, preventing tumor metastasis. Here, we found that a prime-boost vaccination approach using intramuscular DNA vaccine priming, followed by intranasal live-attenuated influenza-vectored vaccine (LAIV) boosting induced higher frequencies of lung CD8+ TRM cells compared with other vaccination regimens. Vaccine-induced lung CD8+ TRM cells, but not circulating memory T cells, conferred significant protection against metastatic melanoma and mesothelioma. Central memory T (TCM) cells induced by the DNA vaccination were major precursors of lung TRM cells established after the intranasal LAIV boost. Single-cell RNA sequencing analysis indicated that transcriptional reprogramming of TCM cells for differentiation into TRM cells in the lungs started as early as day 2 post the LAIV boost. Intranasal LAIV altered the mucosal microenvironment to recruit TCM cells via CXCR3-dependent chemotaxis and induced CD8+ TRM-associated transcriptional programs. These results identified TCM cells as the source of vaccine-induced CD8+ TRM cells that protect against lung metastasis. Significance: Prime-boost vaccination shapes the mucosal microenvironment and reprograms central memory T cells to generate lung resident memory T cells that protect against lung metastasis, providing insights for the optimization of vaccine strategies.

Effective integration of COVID-19 vaccination with routine immunization: A case study from Kinshasa, DRC

BackgroundIn response to the challenge of maintaining COVID-19 vaccination coverage amidst the pandemic, VillageReach, in collaboration with the Ministry of Public Health Prevention and Hygiene in Kinshasa, DRC, integrated COVID-19 vaccination with routine immunization services at two primary healthcare facilities. This initiative, launched in July 2022, represented the first of its kind in the DRC, aiming to assess the effectiveness and scalability of a multimodal vaccination approach. MethodsThrough a rapid appraisal involving key informant interviews and analysis of pre- and post-integration service delivery data, this case study explores the operational dynamics and outcomes of integrating COVID-19 and routine immunizations. ResultsResults demonstrated that the integrated approach not only maintained COVID-19 vaccine coverage but also significantly enhanced routine immunization uptake, particularly among under-immunized and zero-dose children. Overall, the vaccination sites, outreach, and integrated health facilities administered 229,983 (33 %) of COVID-19 vaccines in Kinshasa, of which 53 % were referred by community health workers. Additionally, 998 under-immunized children received routine immunizations, of whom 126 were zero-dose children. Key success factors included sustained community health worker engagement, neighborhood-specific strategies, accessible vaccination points, and robust data management. The findings suggest that such integrative strategies can effectively bolster immunization coverage in urban poor communities, offering valuable insights for similar initiatives in the DRC and beyond. ConclusionThis study advocates for sustained investment in innovative immunization models to strengthen primary healthcare systems post-pandemic.

Immune Responses to Methicillin-Resistant Staphylococcus aureus Infections and Advances in the Development of Vaccines and Immunotherapies.

Staphylococcus aureus (SA) is a major bacterial pathogen and causes a wide range of clinical infections in humans leading to severe outcomes including meningitis, endocarditis, and sepsis. This literature review examines studies on host immune responses after infections with SA and methicillin-resistant Staphylococcus aureus (MRSA) and their immune evasion mechanisms. Furthermore, information about vaccines and immunotherapies against SA and MRSA is reviewed. We found promising toxoid vaccine approaches, which deserve further research. We also found support for antitoxin therapies and immunomodulating therapies as high-potential research areas. Although many promising vaccines and immunotherapy candidates have been studied in animal models, more human clinical studies are needed to confirm their long-term safety and efficacy.

An integrated in silico reverse vaccinology approach for multi-epitope vaccine designing against Shigellosis caused by Shigella flexneri serotype X

An integrated in silico reverse vaccinology approach for multi-epitope vaccine designing against Shigellosis caused by Shigella flexneri serotype X

The Interplay between COVID-19 and Diabetes: Understanding Hyperglycemia, Complications, and Management Challenges in Diabetic Patients

The COVID-19 pandemic has significantly impacted individuals with diabetes, revealing a complex interplay between the virus and pre-existing hyperglycemia. This review explores how COVID-19 exacerbates hyperglycemia in diabetic patients, primarily through mechanisms such as stress response, cytokine storms, and increased insulin resistance. Diabetic individuals are particularly susceptible to severe COVID-19 outcomes, including heightened mortality rates, due to compromised immune responses and coexisting conditions like cardiovascular and renal complications. The review also addresses the unique challenges of managing diabetes during COVID-19, including the need for adjustments in insulin therapy and the impact of COVID-19 treatments, such as corticosteroids, on glucose control. Additionally, it highlights the potential long-term effects of COVID-19 on diabetic patients, including the onset of new diabetes and persistent metabolic issues. The review emphasizes the importance of glycemic control, vaccination, and holistic care approaches to mitigate the severity of COVID-19 in diabetic patients. Furthermore, it examines the psychological and socioeconomic impacts of the pandemic on this vulnerable population. As ongoing research continues to investigate the interaction between COVID-19 and diabetes, this review provides a comprehensive understanding of the challenges and future directions in managing diabetic patients during and after the pandemic. Keywords: COVID-19, Diabetes, Hyperglycemia, Complications, Management Challenges, Diabetic Patients

Clinical Manifestations and Outcomes in Adults Hospitalized With Respiratory Syncytial Virus and Influenza a/B: A Multicenter Observational Cohort Study.

Respiratory syncytial virus (RSV) and influenza cause significant health challenges, particularly for individuals with comorbid conditions and older adults. However, information on the clinical manifestations and outcomes of adults hospitalized with RSV in Europe remains limited. This multicenter observational cohort study of adults hospitalized with RSV or influenza A or B from March 2016 to April 2020 investigated the clinical manifestations, mortality risk factors, and association with 90-day mortality rates by logistic regression analysis after adjustment for covariates. Of 988 patients hospitalized with either virus, 353 had RSV, 347 had influenza A, and 288 had influenza B infection. Patients with RSV, compared with those with influenza A or B, were more likely to have comorbid conditions (83% for RSV vs 72% for influenza A [P = .03] and 74% for influenza B [P = .001]) or pneumonia (41% vs 29% [P = .03] and 24% [P < .001], respectively). After adjustment for covariates, RSV infection was associated with an increased all-cause mortality rate within 90 days compared with influenza B (odds ratio, 2.16 [95% confidence interval, 1.20-3.87]; P = .01) but not influenza A (1.38 [.84-2.29]; P = .21). Increasing age and present pneumonia were identified as independent mortality risk factors in patients with RSV. Older adults hospitalized with RSV infections are at a higher risk of dying within 90 days of hospitalization than patients admitted with influenza B but at a similar risk as those admitted with influenza A, emphasizing the detrimental effects and severity of older patients being infected with RSV. Our findings underscore the need for strategic testing and vaccination approaches to mitigate the impact of RSV among older adults.

Responding to epidemics: the case of the Nguyễn Dynasty, focusing on the period 1802–1883

Abstract In the past, Vietnam was impacted by numerous epidemics, particularly during the Nguyễn Dynasty from 1802 to 1883. Based on data from the Đại Nam Thực Lục (1961) (The Veritable Records of the Great South), this article investigates the frequency and nature of these epidemics, identifies the types of common diseases at that time, and explores the underlying causes of these outbreaks. The study further examines the Nguyễn Dynasty's strategies for managing these health crises. During these outbreaks, the dynasty faced significant challenges, with frequent epidemics leading to high death rates, widespread social disruption, and economic decline. The dynasty's primary preventive measures, heavily reliant on spiritual practices like prayer, highlight the limited medical understanding at the time and the constraints of its socio-political framework. However, there was a progressive shift towards the incorporation of Western medical innovations, particularly in the vaccine approach to treat diseases like smallpox. This transition not only marked a critical evolution in the local healthcare approach but also set the stage for more systematic medical advancements in Vietnam during the colonial period (1884–1945).

Phase II Trial of HER-Vaxx, a B-cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients Under Platinum-Based Chemotherapy (HERIZON).

A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA). Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated. A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52-14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01-9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells. HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.

A Magnetically Driven Biodegradable Microsphere with Mass Production Capability for Subunit Vaccine Delivery and Enhanced Immunotherapy.

Subunit vaccines have emerged as a promising strategy in immunotherapy for combating viral infections and cancer. Nevertheless, the clinical application of subunit vaccines is hindered by limitations in antigen delivery efficiency, characterized by rapid clearance and inadequate cellular uptake. Here, a novel subunit vaccine delivery system utilizing ovalbumin@magnetic nanoparticles (OVA@MNPs) encapsulated within biodegradable gelatin methacryloyl (GelMA) microspheres was proposed to enhance the efficacy of antigen delivery. OVA@MNPs-loaded GelMA microspheres, denoted as OMGMs, can be navigated through magnetic fields to deliver subunit vaccines into the lymphatic system efficiently. Moreover, the biodegradable OMGMs enabled the sustained release of subunit vaccines, concentrating OVA around lymph nodes and enhancing the efficacy of induced immune response. OMGMs were produced through a microfluidic droplet generation technique, enabling mass production. In murine models, OMGMs successfully accumulated antigens in lymph nodes abundant in antigen-presenting cells, leading to enhanced cellular and humoral immunity and pronounced antitumor effects with a single booster immunization. In conclusion, these findings highlight the promise of OMGMs as a practical subunit vaccination approach, thus addressing the limitations associated with antigen delivery efficiency and paving the way for advanced immunotherapeutic strategies.