Vaccines For Infectious Diseases Research Articles

Harnessing T-Cells for Enhanced Vaccine Development against Viral Infections

Despite significant strides in vaccine research and the availability of vaccines for many infectious diseases, the threat posed by both known and emerging infectious diseases persists. Moreover, breakthrough infections following vaccination remain a concern. Therefore, the development of novel vaccines is imperative. These vaccines must exhibit robust protective efficacy, broad-spectrum coverage, and long-lasting immunity. One promising avenue in vaccine development lies in leveraging T-cells, which play a crucial role in adaptive immunity and regulate immune responses during viral infections. T-cell recognition can target highly variable or conserved viral proteins, and memory T-cells offer the potential for durable immunity. Consequently, T-cell-based vaccines hold promise for advancing vaccine development efforts. This review delves into the latest research advancements in T-cell-based vaccines across various platforms and discusses the associated challenges.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.

Vaccine adjuvants for infectious disease in the clinic

AbstractAdjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.Translational impact statementIn the aftermath of the COVID‐19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

Vaccine Hesitancy Prediction Based on Machine Learning Algorithms

Modern medical technology has led to the development and implementation of vaccines for various infectious or malignant diseases, offering active acquired immunity to those who receive them. Despite extensive research and validation confirming vaccine safety, a segment of the population exhibits reluctance or refusal to get vaccinated, known as vaccine hesitancy. This hesitancy posed challenges during the COVID-19 pandemic, hindering the attainment of herd immunity and contributing to a higher number of preventable deaths. It is imperative to accurately predict vaccine hesitancy by analyzing various population characteristics to distinguish between those with and without vaccine hesitancy. Subsequently, different communication strategies and incentives can be adopted. In this article, the author utilizes private data from a survey that includes demographic features about the participants, as well as their behaviors and beliefs about the COVID-19 pandemic and vaccination. To identify the most significant features, the author employed the feature importance method to eliminate features that were less influential and narrowed to the 17 most influential features. Machine learning techniques, including non-ensemble, ensemble, and neural networks, were employed to predict the data set and then calculate testing errors to compare each method on prediction accuracy. The authors concluded that neural networks have superior prediction accuracy and are mostly immune to overfitting. Although neural networks take a long time to train, the test error of less than 5.5% is significantly lower than the 6.5% average error of other methods.

Trans-amplifying RNA expressing functional miRNA mediates target gene suppression and simultaneous transgene expression

The co-delivery of microRNAs (miRNAs) and protein-coding RNA presents an opportunity for a combined approach to gene expression and gene regulation for therapeutic applications. Protein delivery is established using long mRNA, self- and trans-amplifying RNA (taRNA), while miRNA delivery typically uses short synthetic oligonucleotides rather than incorporating it as a precursor into long RNA. Although miRNA delivery into the cell cytoplasm using long genomes of RNA viruses has been described, concerns have remained regarding low processing efficiency. However, miRNA precursors can be released from long cytoplasmic alphaviral RNA by a cytoplasmic fraction of Drosha. taRNA, a promising vector platform for infectious disease vaccination, employs a non-replicating mRNA expressing an alphaviral replicase to amplify a protein-coding short transreplicon-RNA (STR) in trans. To investigate the possibility of simultaneously delivering protein expression and gene silencing, we tested whether a taRNA system can carry and release functional miRNA to target cells. Here we show that mature miRNA is released from STRs, and silences specific targets in a replication-dependent manner for several days without compromising the expression of STR-encoded proteins. Our findings suggest that incorporating miRNAs into the taRNA vector platform has the potential for gene regulation alongside the expression of therapeutic genes.

The Association of Vaccination for Common Adult Infectious Diseases and Uptake of COVID-19 Vaccines among 5,006,851 Veterans, 20 December 2020-31 October 2021.

Disparities in vaccination coverage for coronavirus disease 2019 (COVID-19) in the United States (U.S.) are consistent barriers limiting our ability to control the spread of disease, particularly those by age and race/ethnicity. This study examines the association between previous vaccination for common adult infectious diseases and vaccination for SARS-CoV-2 among a cohort of veterans in the U.S. Sociodemographic and clinical data were utilized from three databases within the Veterans Health Administration included in the electronic health record. We examined the association of previous vaccination for common adult vaccinations through six separate multivariable logistic regression analyses, one for each previous vaccine exposure, adjusting for demographic and clinical variables. We also examined the association of receiving any one of the six common adult vaccinations and vaccination against SARS-CoV-2. Adjusted models indicate higher odds of vaccination for SARS-CoV-2 among those who received each of the previous vaccinations. Significant differences were also noted by race/ethnicity and age. Veterans who recorded receiving any one of the previous vaccinations for common adult infections had significantly greater odds of receiving any vaccination against SARS-CoV-2. Understanding veterans' previous vaccination status can assist researchers and clinicians in impacting the uptake of novel vaccines, such as vaccination against SARS-CoV-2.

Nanoparticle-Conjugated Toll-Like Receptor 9 Agonists Improve the Potency, Durability, and Breadth of COVID-19 Vaccines.

Development of effective vaccines for infectious diseases has been one of the most successful global health interventions in history. Though, while ideal subunit vaccines strongly rely on antigen and adjuvant(s) selection, the mode and time scale of exposure to the immune system has often been overlooked. Unfortunately, poor control over the delivery of many adjuvants, which play a key role in enhancing the quality and potency of immune responses, can limit their efficacy and cause off-target toxicities. There is a critical need for improved adjuvant delivery technologies to enhance their efficacy and boost vaccine performance. Nanoparticles have been shown to be ideal carriers for improving antigen delivery due to their shape and size, which mimic viral structures but have been generally less explored for adjuvant delivery. Here, we describe the design of self-assembled poly(ethylene glycol)-b-poly(lactic acid) nanoparticles decorated with CpG, a potent TLR9 agonist, to increase adjuvanticity in COVID-19 vaccines. By controlling the surface density of CpG, we show that intermediate valency is a key factor for TLR9 activation of immune cells. When delivered with the SARS-CoV-2 spike protein, CpG nanoparticle (CpG-NP) adjuvant greatly improves the magnitude and duration of antibody responses when compared to soluble CpG, and results in overall greater breadth of immunity against variants of concern. Moreover, encapsulation of CpG-NP into injectable polymeric-nanoparticle (PNP) hydrogels enhances the spatiotemporal control over codelivery of CpG-NP adjuvant and spike protein antigen such that a single immunization of hydrogel-based vaccines generates humoral responses comparable to those of a typical prime-boost regimen of soluble vaccines. These delivery technologies can potentially reduce the costs and burden of clinical vaccination, both of which are key elements in fighting a pandemic.

Issues with infectious disease vaccine introduction into routine vaccination in Japan, and considerations for accelerating the process

Routine vaccinations help prevent the outbreak and spread of infectious diseases; however, it can take up to ten years from vaccine approval to introduction into routine vaccination schedules in Japan. Here, we investigate the information required to introduce an approved vaccine into routine vaccination schedules and the reasons why it takes so long. Based on the published data of the Immunization and Vaccine Committee of the Health Science Council, we set out to explore ways to facilitate discussion on this topic. The following issues were identified as discussion points: disease burden, efficacy and safety, and cost-effectiveness. Until now, epidemiological information has been used to evaluate the efficacy of vaccines, and also to evaluate the safety in the presence of notable adverse reactions. However, in some cases, it took a long time to obtain epidemiological information regarding the frequency of rare but serious adverse reactions and the need for a booster dose. Given the risk of spreading infectious diseases due to delays in decision-making, vaccines may have to be introduced into routine vaccination schedules based on the results of clinical trials that can be obtained in a relatively short period. In contrast, epidemiological information is necessary to evaluate the disease burden, frequency of adverse reactions, and the necessity of booster doses. Therefore, developing an epidemiological information collection system is urgently required.

SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients.

Vaccinations, for example flu vaccine, may be a cause of cross-reactive immunostimulation that prevents a larger spectrum of infections. However, whether SARS-CoV-2 vaccinations may also determine this effect is unclear. This study aims, first, to assess the incidence of infections at hospital admission and during the hospitalization in older inpatients vaccinated and unvaccinated against SARS-CoV-2; second, to compare length of hospital stay and in-hospital mortality between vaccinated and unvaccinated individuals. This retrospective study included 754 older inpatients admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. Sociodemographic and health-related data, and the diagnosis of infections at hospital admission and during hospitalization were collected from medical records. The sample's mean age was 87.2years, 59.2% were females, and 75.5% were vaccinated against SARS-CoV-2. Vaccinated individuals had 36% lower odds of intra-hospital infections (OR = 0.64, 95%CI 0.44-0.94) and 39% lower in-hospital death (HR = 0.61, 95%CI 0.39-0.95), also after adjusting for potential confounders, while no significant results emerged about infections at hospital admission. Considering the hospitalization's endpoints, SARS-CoV-2 vaccination was associated with a lower probability of being transferred to long-term care or other hospital departments than returning home (OR = 0.63, 95%CI 0.40-0.99). In older inpatients, SARS-CoV-2 vaccination seems to be associated with a lower likelihood of intra-hospital infectious diseases not caused by SARS-CoV-2 and all-cause in-hospital mortality. The vaccination coverage in the older population could limit not only the onset and severity of COVID-19 but also the occurrence of other infectious diseases.

Current development of therapeutic vaccines for the treatment of chronic infectious diseases.

Chronic infectious diseases refer to diseases that require a long period of time from onset to cure or death, the use of therapeutic vaccines has recently emerged to eradicate diseases. Currently, clinical research is underway to develop therapeutic vaccines for chronic infectious diseases based on various vaccine formulations, and the recent success of the messenger RNA vaccine platform and efforts to apply it to therapeutic vaccines are having a positive impact on conquering chronic infectious diseases. However, since research on the development of therapeutic vaccines is still relatively lacking compared to prophylactic vaccines, there is a need to focus more on the development of therapeutic vaccines to overcome threats to human health caused by chronic infectious diseases. In order to accelerate the development of therapeutic vaccines for chronic infectious diseases in the future, it is necessary to establish a clear concept of therapeutic vaccines suitable for the characteristics of each chronic infectious disease, as well as standardize vaccine effectiveness evaluation methods, secure standards/reference materials, and simplify the vaccine approval procedure.

The United Nation's Civil Assistance Command in Korea's (UNCACK) Public Health Measures on Koje Island during the Korean War.

This study focuses on the health and sanitation projects carried out on Koje Island by the United Nations Civil Assistance Command in Korea (UNCACK). Koje Island was unique as it served as a destination for dispersed refugees and as an area for housing prisoners of war. Unlike in other regions, UNCACK was actively involved in the implementation of health and sanitation projects on Koje Island. Their infectious disease control projects on Koje Island serve as a valuable example for studying infectious disease prevention initiatives and local medical projects in modern and contemporary Korea. In this study, I examine the documents produced by UNCACK to assess the status of infectious disease control and vaccination plans. Additionally, I analyze the disease prevention initiatives implemented among the residents of Koje Island, including isolation, treatment, and improvement of living conditions. Finally, I explore the characteristics of the Koje Island preventive measures and assess the efforts and limitations of both UNCACK and the Korean government in addressing health issues during the Korean War. Despite the presence of refugees and POWs, Koje Island managed to implement systematic public health initiatives in a controlled environment, widely regarded as highly successful. The public health initiatives on Koje Island, led by UNCACK, provided an opportunity to utilize limited resources, manpower, and Korean health professionals, cultivating the skills necessary to manage infectious diseases effectively. Moreover, these initiatives on Koje Island, although modest, continued into the postwar period, influencing medical missionary activities, the demand for health services among residents, the establishment of independent medical institutions, and the implementation of local health projects.

Mechanism, applications and of mRNA vaccines

In recent years, infectious diseases such as novel coronavirus pneumonia, influenza, and tuberculosis have brought great social and economic burdens to the world. Vaccination is the most effective and economical intervention to control the spread of infectious diseases, save lives and protect people's health. mRNA vaccine is expected to be a new type of infectious disease vaccine. Compared with traditional vaccines, mRNA vaccines have many advantages, such as high efficiency, safety, short production cycle, low cost, etc. However, the stability of mRNA vaccines is poor. However, mRNA vaccines have poor stability and low delivery efficiency, and their clinical applications are greatly restricted. Therefore, current and future research focuses on the design of advanced and tolerable delivery systems to improve the efficiency of antigen expression and presentation, as well as the optimization of mRNA structure to prolong and control the duration of expression, under the premise of ensuring the safety of vaccines. This review summarizes the history, classification, principles and mechanisms of mRNA vaccines, and briefly discusses the current challenges and future directions for developing mRNA vaccines for different diseases.

Evaluation of the efficacy, safety and influencing factors of concomitant and sequential administration of viral respiratory infectious disease vaccines: a systematic review and meta-analysis.

There is no clear conclusion on the immunogenicity and adverse events of concomitant administration the viral respiratory infectious disease vaccines. We aimed to evaluate the impact of concomitant administering viral respiratory infectious disease vaccines on efficiencies, safety and influencing factors. This meta-analysis included studies from PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, WHO COVID-19 Research, and ClinicalTrials.gov databases. Randomized controlled trials of the adult participants concomitant administered with viral respiratory infectious disease vaccine and other vaccines were included. The main outcomes were the seroconversion rate and seroprotection rate of each vaccine. Used the Mantel-Haenszel fixed effects method as the main analysis to estimate the pooled RRs and the corresponding 95% confidence intervals. The risk of bias for each trial was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, while evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A total of 21 studies comprising 14060 participants with two types of vaccines were retained for the meta-analysis. Concomitant immunization reduced the geometric mean titer (RR: 0.858, 95% CI: (0.785 to 0.939)) and the geometric mean fold rise (0.754 (0.629 to 0.902)) in the SARS-COV-2 vaccine group but increased the seroconversion rate (1.033 (1.0002 to 1.067)) in the seasonal influenza vaccine group. Concomitant administration were influenced by the type of vaccine, adjuvant content, booster immunization, and age and gender of the recipient. This meta-analysis suggested that the short-term protection and safety of concomitant administered were effective. Appropriate adjuvants, health promotion and counselling and booster vaccines could improve the efficiency and safety of Concomitant vaccination. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022343709.

Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern

COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. Here we tested an intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 compared with the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum, in mice, for immunological read-outs. The same formulation delivered I.N. or S.C. was tested in hamsters to assess efficacy. I.N. vaccination improved systemic T cell responses compared to an equivalent dose of antigen delivered S.C. and T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralising the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralising capacity against multiple variants of concern (VOC), compared to S.C. vaccination. I.N. vaccination provided significant protection from lung pathology compared to unvaccinated animals upon challenge with homologous and heterologous SARS-CoV-2 strains in a hamster model. These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralising antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases. This study was funded by Duke-NUS Medical School, the Singapore Ministry of Education, the National Medical Research Council of Singapore and a DBT-BIRAC Grant.

Thiolated chitosan encapsulation constituted mucoadhesive nanovaccine confers broad protection against divergent influenza A viruses

Influenza A virus (IAV) poses a significant threat to human and animal health, necessitating the development of universal influenza vaccines that can effectively activate mucosal immunity. Intranasal immunization has attracted significant attention due to its capacity to induce triple immune responses, including mucosal secretory IgA. However, inducing mucosal immunity through vaccination is challenging due to the self-cleansing nature of the mucosal surface. Thiolated chitosan (TCS) were explored for mucosal vaccine delivery, capitalizing on biocompatibility and bioadhesive properties of chitosan, with thiol modification enhancing mucoadhesive capability. The focus was on developing a universal nanovaccine by utilizing TCS-encapsulated virus-like particles displaying conserved B-cell and T-cell epitopes from M2e and NP proteins of IAV. The optimal conditions for nanoparticle formation were investigated by adjusting the thiol groups content of TCS and the amount of sodium tripolyphosphate. The nanovaccine induced robust immune responses and provided complete protection against IAVs from different species following intranasal immunization. The broad protective effect of nanovaccines can be attributed to the synergistic effect of antibodies and T cells. This study developed a universal intranasal nanovaccine and demonstrated the potential of TCS in the development of mucosal vaccines for respiratory infectious diseases.

Development and evaluation of a bivalent vaccine based on recombinant newcastle disease virus expressing infectious bursal disease virus VP2L-CH3-CH4 in SPF chickens

Newcastle disease (ND) and infectious bursal disease (IBD) are two viral infectious diseases that are extremely damaging to the poultry industry and are widespread throughout the world. It is necessary to develop a safe and effective vaccine against IBD and ND because vaccination is an effective preventive measure. It has been discovered that recombinant proteins expressed by an expression system in which a fragment of mammalian Immunoglobulin G (IgG) Fragment crystallizable (Fc) is linked to a segment of a gene have antibody-like properties that increase the exogenous protein's serum half-life. Heavy chain constant region 3 and heavy chain constant region 4 (CH3-CH4) of Avian Immunoglobulin Y (IgY) is structurally very similar to mammalian Ig G Fc. In this study, a bivalent vaccine rClone30-VP2L-CH3-CH4-GMCSF was developed by using NDV rClone30-chGM-CSF vector to produce VP2L-CH3-CH4 fusion protein. The vaccine has been given to 14-day-old specific pathogen free (SPF) free chickens to test whether it has the potential to prevent IBD and ND. Anti-IBDV and anti-NDV antibody levels in serum were evaluated using ELISA and HI, respectively, and the contents of CD4+ T, CD8+ T, and B cells in leukocytes were determined via flow cytometry. The contents and mRNA transcription levels of four inflammatory factors, IL-1β, IL-4, IFN-γ and chGM-CSF, were detected by ELISA and real-time PCR respectively. The results showed that after vaccination with the rClone30-VP2L-CH3-CH4-GMCSF vaccine, the levels of anti NDV and anti IBDV antibodies in chickens were significantly higher than those of the rClone30 vaccine and commercial vaccines. Meanwhile, the contents and transcription levels of inflammatory factors in chickens inoculated with rClone30-VP2L-CH3-CH4-GMCSF were significantly increased, and the proliferation response of B cells, CD4+ and CD8+ T cells was also stronger. However, the rClone30-VP2L-CH3-CH4-GMCSF vaccine had no significant advantage over the rClone30-VP2L-GMCSF vaccine in any of the above-mentioned features. In summary, rClone30-VP2L-CH3-CH4-GMCSF can stimulate the body to produce a stronger immune response, showing its potential to be considered as vaccine against IBD and ND, but the addition of CH3-CH4 did not improve the vaccine's immune effect as expected. The research lays the foundation for developing vaccines for other infectious viral diseases and avoids a unrealistic vaccine optimization method.

Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters

DNA vaccines for infectious diseases and cancer have been explored for years. To date, only one DNA vaccine (ZyCoV-D) has been authorized for emergency use in India. DNA vaccines are inexpensive and long-term thermostable, however, limited by the low efficiency of intracellular delivery. The recent success of mRNA/lipid nanoparticle (LNP) technology in the COVID-19 pandemic has opened a new application for nucleic acid-based vaccines. Here, we report that plasmid encoding a trimeric spike protein with LNP delivery (pTS/LNP), similar to those in Moderna's COVID-19 vaccine, induced more effective humoral responses than naked pTS or pTS delivered via electroporation. Compared to TSmRNA/LNP, pTS/LNP immunization induced a comparable level of neutralizing antibody titers and significant Th1-biased immunity in mice; it also prolonged the maintenance of higher antigen-specific IgG and neutralizing antibody titers in hamsters. Importantly, pTS/LNP immunization exhibits enhanced cross-neutralizing activity against SARS-CoV-2 variants and protects hamsters from the challenge of SARS-CoV-2 (Wuhan strain and omicron BA.1 variant). This study indicates that pDNA/LNPs as a promising platform could be a next-generation vaccine technology.

269. Reference Data of Biochemical and Hematology Parameters in Juvenile and Adult Owl Monkeys (Aotus nancymaae) for Biomedical Research

Abstract Background Non-human primates (NHP), including New World monkeys (NWM), are used in varied fields of biomedical research encompassing infectious disease, behavioral sciences and drug and vaccine development. In these studies, normal reference values for biochemical and hematological parameters are often needed for comparison with experimental results. These blood parameters are useful guides in reaching a diagnosis, estimating the prognosis of the disease and monitoring the progress of treatment. Although there are various reports of biochemical and hematologic parameters in Old World monkeys, the range of reference values often differs between NHP species. Despite the importance of NWMs such as Aotus nancymaae in biomedical research, few studies have examined these values and with a limited number of animals only. A. nancymaae is widely used for research and often used to study the principal types of human malaria (P. falciparum and P. vivax). These primates have also been used to study leishmaniasis, schistosomiasis, tuberculosis and various types of enteric infections. Furthermore, in recent years oral challenge models have been developed in A. nancymaae for Campylobacter jejuni, Shigella flexneri, and Enterotoxigenic Escherichia coli (ETEC). However, there is no updated data on biochemical and hematological parameters for A. nancymaae. Therefore, the aim of this study was to provide complete and accurate reference intervals of biochemical and hematological values to assess the health status indices of A. nancymaae housed in a vivarium prior to their use. Methods To characterize these parameters, a total of 1250 blood samples (1003 from juvenile and 247 from adult monkeys) were analyzed between 2007 to 2022. A total of 14 biochemical and 20 hematology parameters were measured. Results A significant change was observed in the values of alkaline phosphatase (ALP), potassium (K+), glucose (GLU), blood urea nitrogen (BUN), creatinine (CRE), hemoglobin (HGB) and lymphocyte (LYM) in relation to sex and age. Conclusion In conclusion, this work establishes a comprehensive and systematic reference of serum biochemical and hematological parameters for A. nancymaae based on a large cohort which can be used to inform and guide future studies utilizing this animal model. Disclosures All Authors: No reported disclosures

Improving Middle-Income Countries Access to Vaccines. A Blueprint to Overcome Current Challenges.

The Global Health Consortium at Florida International University developed an end-to-end solution framework based on the input of a diverse panel of experts from middle-income country (MIC) government agencies, public health think tanks, academia, and nonprofit organizations to identify mechanisms to help MIC governments and stakeholders increase access to novel vaccines for infectious diseases. The resultant layout can be deployed to improve vaccine discovery and development, strengthen regulatory processes, and boost vaccine production, access, and implementation. Mechanisms include policies and incentives MIC governments can use to stimulate vaccine investment and activity, as well as actions government agencies can take together with other stakeholders to coordinate efforts or build capabilities. Through a series of individual virtual interviews, we engaged diverse experts from MIC government agencies, public health think tanks, academia, and nonprofit organizations who understand the vaccine ecosystem, immunization policies, and population health financing at global, regional, and country levels. Responses were mapped, and in-depth questions were prepared for a group virtual discussion. This paper is the result of such a group discussion. The panel identified clear opportunities for MICs to improve locally-driven innovations and future access to novel vaccines. It proposes a solution framework for countries considering investing in vaccine research and development and innovation to use as a guide to evaluate the steps they could take to improve such an environment and incentivize innovation in vaccine development. It is hoped that this end-to-end solution framework will become a key resource to help MICs strengthen policies and take more actions to make such improvements.

Immunoinformatics study to explore dengue (DENV-1) proteome to design multi-epitope vaccine construct by using CD4+ epitopes

BackgroundImmunoinformatics is an emerging interdisciplinary field which integrates immunology, bioinformatics, and computational biology to study the immune system. In this study, we apply immunoinformatics approaches to explore the dengue proteome in order to design a multi-epitope vaccine construct. MethodsWe used existing databases and algorithms to predict potential epitopes on dengue proteins and used a bioinformatics approach to identify the most promising epitopes. We then used molecular modelling to develop a multi-epitope construct which could be used as a potential vaccine. The results of this study demonstrate that immunoinformatics is a powerful tool for exploring and designing potential vaccines for infectious diseases like dengue. ResultsHere, we found four CD4+ epitopes NLKYSVIVTVHTGDQ, ANPIVTDKEKPVNIE, LDPVVYDAKFEKQL, and VGAIALDFKPGTSGS that were used to design vaccine construct. The vaccine construct docked with TLR5. RMSD values suggest that docked complex of TLR5 and vaccine construct have putative stable interaction to induce immunogenic effects on host. ConclusionsFurthermore, our study provides a proof of concept for the use of immunoinformatics approaches in DENV vaccine design. This vaccine can be effective in treating patients infected with DENV virus.