Disease Vaccine Research Articles

Sustainable integration of artificial intelligence and machine learning approaches within the African infectious disease vaccine research and development ecosystem

Artificial Intelligence and Machine Learning (AI/ML) techniques, including reverse vaccinology and predictive models, have already been applied for developing vaccine candidates for COVID-19, HIV, and Hepatitis, streamlining the vaccine development lifecycle from discovery to deployment. The application of AI and ML technologies for improving heath interventions, including drug discovery and clinical development, are expanding across Africa, particularly in South Africa, Kenya, and Nigeria. Further initiatives are required however to expand AI/ML capabilities across the continent to ensure the development of a sustainable ecosystem including enhancing the requisite knowledge base, fostering collaboration between stakeholders, ensuring robust regulatory and ethical frameworks and investment in requisite infrastructure.

Introduction about Global infectious disease and use of nanotechnology

Infectious diseases, including COVID-19, malaria, tuberculosis, and sexually transmitted diseases (STDs), pose significant threats to global health. Nanotechnology has emerged as a promising tool in the diagnosis, treatment, and prevention of these diseases. This review highlights the applications of nanotechnology in combating infectious diseases. Nanoparticles, such as metallic nanoparticles, liposomes, and quantum dots, have been employed in the detection and treatment of infectious diseases. Nanotechnology-based drug delivery systems have improved the efficacy and reduced the toxicity of antiviral and antibacterial drugs. Additionally, nanotechnology has enabled the development of point-of-care diagnostics and vaccines for infectious diseases. This review provides an overview of the current state of nanotechnology in infectious disease management and highlights its potential to revolutionize the field. By leveraging the unique properties of nanoparticles, nanotechnology can provide innovative solutions for the diagnosis, treatment, and prevention of infectious diseases, ultimately improving global health outcomes. Keywords: Nanotechnology, Infectious diseases, COVID-19, Malaria, Tuberculosis, HIV/AIDS

Allergen-Specific Immunotherapy and Trained Immunity.

The high prevalence of allergic diseases reached over the last years is attributed to the complex interplay of genetic factors, lifestyle changes, and environmental exposome. Allergen-specific immunotherapy (AIT) is the single therapeutic strategy for allergic diseases with the potential capacity to modify the course of the disease. Our knowledge of the mechanisms involved in allergy and successful AIT has significantly improved. Recent findings indicate that long-term allergen tolerance upon AIT discontinuation not only relies on the generation of proper adaptive immune responses by the generation of allergen-specific regulatory T and B cells enabling the induction of different isotypes of blocking antibodies but also relies on the restoration of proper innate immune responses. Trained immunity (TRIM) is the process by which innate immune cells acquire memory by mechanisms depending on metabolic and epigenetic reprogramming, thus conferring the host with increased broad protection against infection. This concept was initially explored for infectious diseases, as well as for vaccination against infections, but compelling experimental evidence suggests that TRIM might also play a role in allergy and AIT. Hyperinflammatory innate immune responses in early life, likely due to TRIM maladaptations, lead to aberrant type 2 inflammation-enhancing allergy. However, exposure to farming environments and specific microbes prevents recurrent infections and allergy development, likely due to mechanisms partially depending on TRIM. TRIM-based vaccines and next-generation AIT vaccines inducing metabolic and epigenetic reprogramming in innate immune cells and their precursors have shown protective antiallergic effects. A better understanding of the factors involved in early-life TRIM mechanisms in the context of allergy and the identification and characterization of novel tolerance inducers might well enable the design of alternative TRIM-based allergen vaccines for allergic diseases.

A Systematic Review on the Impact of Vaccination for Respiratory Disease on Antibody Titer Responses, Health, and Performance in Beef and Dairy Cattle

Bovine respiratory disease (BRD) is a multifactorial disease complex commonly affecting beef and dairy operations. Vaccination against major BRD-related pathogens is routinely performed for disease prevention; however, uniform reporting of health and performance outcomes is infrequent. Our objective was to evaluate the effect of commercially available BRD-pathogen vaccination on titer response with respect to health or performance in beef and dairy cattle. This study was conducted under Prisma 2020 guidelines for systematic reviews and PRESS guidelines utilizing five databases. Criteria for study inclusion were as follows: research conducted in the USA or Canada, between 1982 and 10 October 2022, on beef or dairy cattle, using a commercially available vaccine labeled for a respiratory pathogen of interest, which evaluated antibody titers alongside either performance or morbidity. A total of 3020 records underwent title and abstract evaluation. Full-text analysis was conducted on 466 reports; 101 studies were included in the final review. Approximately 74% of included studies were beef cattle-based versus 26% dairy cattle-based. This review aimed to assess how vaccination titer responses affect beef and dairy cattle health and performance, but varying study methods made comparisons difficult, highlighting the need for consistent reporting.

Development of a genotype-matched Newcastle disease DNA vaccine candidate adjuvanted with IL-28b for the control of targeted velogenic strains of Newcastle disease virus in Africa

Newcastle disease virus (NDV) is an extremely contagious and deadly virus that affects numerous bird species, posing serious threats to poultry production on a global scale. In addition to implementing biosecurity practices in farming systems, vaccination remains the most effective means of controlling Newcastle disease (ND). However, while existing commercial vaccines provide some level of protection, the effectiveness of these vaccines can be questionable, particularly in field settings where the complexity of vaccination program implementation poses significant challenges, especially against virulent genotypes of NDV. A genotype-matched NDV DNA vaccine could potentially offer a more effective vaccination approach than currently available live attenuated vaccines. By being specifically tailored to match circulating strains, such a vaccine might improve efficacy and reduce the risk of vaccine failure due to genotype mismatch. To develop an alternative vaccine approach, two ND DNA vaccines were constructed in this study. Each vaccine developed in this study contains the fusion (F) and haemagglutinin-neuraminidase (HN) genes of a virulent NDV genotype VII isolate from Tanzania. Interferon lambda-3 (IFNλ3; IL-28b), which has demonstrated capacity to significantly enhance specific adaptive immune responses and decreased levels of inflammatory cytokines, as well as improved protective responses at a high viral challenge dose, was included in one of the developed vaccines. These plasmids were designated pTwist-F-HN-VII-IL28b and pTwist-F-HN-VII. The two plasmids differed in that pTwist-F-HN-VII-IL28b contained the cytokine adjuvant IL-28b. Transfection of cells and subsequent immunofluorescence assays indicated that both plasmids expressed high levels of NDV F-HN proteins. In vivo immunization demonstrated that chicks intramuscularly immunized with pTwist-F-HN-VII-IL28b exhibited significant immune responses compared to chicks immunized with pTwist-F-HN-VII or the commonly used LaSota vaccine (LaSota), which was used as a control. The protective efficacy of pTwist-F-HN-VII-IL28b was 80% after challenge with the highly virulent NDV strain ON148423, compared to 60% for chicks vaccinated using LaSota, and pTwist-F-HN-VII. The findings of this study indicate that IL-28b can be employed as a molecular adjuvant for NDV vaccines. This study represents a key milestone in Newcastle disease vaccine research, particularly in the development of a genotype-matched DNA vaccine candidate. Additionally, this study demonstrated that the combination of F, HN, and IL-28b elicits an efficacious immune response against virulent NDV strains.

Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination. Data from a large phase 2 randomized double-blind clinical trial (PREVAC) were used to evaluate waning of anti-Ebola virus (EBOV) glycoprotein (GP1,2) antibody concentrations after rVSVΔG-ZEBOV-GP or Ad26.ZEBOV, MVA-BN-Filo vaccination with linear mixed-effect regression models. After a post-vaccination peak, each vaccination strategy was associated with a decrease of anti-EBOV GP1,2 antibody concentrations with distinct kinetics, highlighting a less-rapid decline in antibody levels after vaccination by rVSVΔG-ZEBOV-GP. One year after administration of the vaccine, antibody concentrations were higher in children compared to adults for both vaccines, although with different effect sizes: 1.74-fold higher concentrations (95% confidence interval [CI] [1.48; 2.02]) for children 12–17 years old to 3.10-fold higher concentrations (95% CI [2.58; 3.69]) for those 1–4 years old compared to adults for Ad26.ZEBOV, MVA-BN-Filo versus 1.36-fold (95% CI [1.12; 1.61]) to 1.41-fold (95% CI [1.21; 1.62]) higher at month 12 higher than these values for adults, with relatively small changes from one age category of children to another for rVSVΔG-ZEBOV-GP. Antibody concentrations also differed according to geographical location, pre-vaccination antibody concentration, and sex. In combination with knowledge on memory response, characterization of the major determinants of immune response durability of both vaccinations may guide future EVD control protocols. Trial registration: ClinicalTrials.gov identifier: NCT02876328..

Impact of COVID-19 disease and COVID-19 vaccinations on hospital admissions for neurological diseases in the Lombardia over-12 population. Data from a self-controlled case series analysis.

The influence of COVID19 vaccination on the risk of different neurological diseases has been subject of intense investigation. No large scale results have been published so far in the population of around 10 million people of Lombardia in Italy. Linkable administrative health databases from the Lombardia region were used. By using the adapted self controlled case series (SCCS) method for event dependent exposures, we estimated the relative incidence of different neurological diseases following pre-specified windows at risk after vaccination and after COVID-19 infection in the over-12 population of Lombardia. Follow-up time before vaccination (Pre-Vax period) was compared with follow-up time 0-28days (high-risk period) from the day of vaccination as well as for COVID infection. The SCCS model was fitted using a conditional Poisson regression model to estimate the relative incidences (RI) and their 95% Confidence Intervals (CI). The 28-day post-vaccination period was associated with a significant increase in the occurrence of ischemic stroke, cerebral haemorrhage, TIAs and myelitis (IRR 1.44, 1.50, 1.67 and 2.65 respectively). When the risk conferred by COVID19 infection was assessed in the same cohort, significant IRR were greater in the occurrence of ischemic stroke, cerebral haemorrhage, and TIAs (IRR 5.6, 3.62, 6.83) and includes also Multiple Sclerosis, neuromyelitis, and polymyositis (5.25, 8.81, 5.67). Our data suggest that the increased risk of non-inflammatory CNS disorders following COVID-19 vaccination is lower than the risk conferred by COVID-19 infection, and that COVID-19 infection increases the risk of some inflammatory and non inflammatory neurological disorders.

Personalized neoantigen-based therapeutic cancer vaccines

Abstract. Tumor neoantigens are new unknown proteins or peptides encoded by somatic gene mutations, also known as tumor-specific antigens (TSAs). They are located on the surface of tumor cells and are only expressed in tumor cells. Cancer vaccines targeting neoantigens can not only effectively induce immune response, but also have the advantages of high safety and fewer side effects, so it has gradually become a research hotspot in tumor therapy. During the current clinical trials, neoantigen-based personalised tumour therapeutic vaccines have shown excellent experimental results and have also proved to be positively helpful for tumour cancer treatment. However, considering that the heterogeneity of tumours increases the uncertainty of the efficacy of disease vaccines, and the time-consuming and complicated preparation process of personalized vaccines, the research and development of personalized oncology therapeutic vaccines based on neoantigens still need different explorations and attempts.

The New Era of mRNA Vaccines: The Success of the Covid-19 Vaccines and the Safety Concerns in Adolescents

Abstract A remarkable scientific achievement during the Covid pandemic is the rapid development and deployment of the mRNA vaccines which played a crucial role in reducing the Covid-related morbidity and mortality. The first-time safe use of the mRNA vaccine platform in humans opened up a new era in vaccinology. In the near future, the mRNA vaccine platform is likely to be used for other diseases as well. Though the Covid mRNA vaccine has been found to be safe in children, a matter of concern is the rare adverse event myocarditis, which was mostly observed among male adolescents. In this setting, we briefly discuss mRNA vaccine-related myocarditis and suggest that the safety concerns need to be alleviated by larger studies with long-term follow-up. We also stress the need for the generation of safety data from children in lower- and middle-income countries as there is limited experience with mRNA vaccines in such settings. The underlying mechanisms need to be understood well as the mRNA vaccine platform holds enormous promise for the future development of vaccines for several diseases.

Immune Checkpoint Inhibitors and Vaccination: Assessing Safety, Efficacy, and Synergistic Potential.

Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients-largely developed in the context of cytotoxic therapies-becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce. Notably, the combination of ICIs with infectious disease vaccines does not appear to exacerbate immune-related adverse events, despite the heightened cytokine activity observed. However, the efficacy of vaccines administered alongside ICIs in preventing infectious diseases remains poorly supported by robust evidence. Preliminary findings suggest a potential survival benefit in cancer patients receiving ICI therapy alongside influenza or SARS-CoV-2 vaccination, though the quality of evidence is currently low. Moreover, the synergistic potential of combining therapeutic cancer vaccines, particularly mRNA-based vaccines, with ICIs indicates promise but with a paucity of phase III data to confirm efficacy. This review critically examines the safety and efficacy of combining ICIs with both infectious disease vaccines and therapeutic cancer vaccines. While vaccination appears safe in patients undergoing ICI therapy, the impact on infectious disease prevention and cancer treatment outcomes warrants further rigorous investigation.

Oral Administration of Zinc Sulfate with Intramuscular Foot-and-Mouth Disease Vaccine Enhances Mucosal and Systemic Immunity.

Background/Objectives: Foot-and-mouth disease (FMD) remains a significant global threat to livestock farming. Current commercial FMD vaccines present several challenges, including the risk of infection and adverse injection site reactions due to oil-based adjuvants. The complex immune environment of the gut-associated lymphoid tissue has the potential to induce broad and diverse immune responses. Therefore, we aimed to explore the potential of zinc sulfate as an oral adjuvant to enhance intestinal mucosal immunity and complement the effects of intramuscular (IM) FMD vaccination. Methods: We conducted serological analyses on mice and pigs, measuring secretory IgA (sIgA) levels and evaluating the expression of mucosal immunity-related genes in pigs. These assessments were used to investigate the systemic and mucosal immune responses induced by oral zinc sulfate administration in combination with an IM FMD vaccine. Results: This combination strategy significantly increased structural protein antibody titers and virus neutralization titers in experimental animals (mice) and target animals (pigs) across early, mid-, and long-term periods. Additionally, this approach enhanced the expression of key cytokines associated with mucosal immunity and increased sIgA levels, which are critical markers of mucosal immunity. Conclusions: Oral zinc sulfate administration may synergize with inactivated FMD vaccines, leading to sustained and enhanced long-term immune responses. This novel strategy could reduce the frequency of required vaccinations or allow for a lower antigen dose in vaccines, effectively stimulating the mucosal immune system and boosting systemic immunity. This approach has the potential to improve the overall efficacy of commercial FMD vaccines.

Motivation, Cues to Action, and Barriers to COVID-19 Vaccine Uptake: A Qualitative Application of the Health Belief Model among Women in Rural Zambia.

Vaccine hesitancy has played a major role in slowing the global COVID-19 response. Using cross-sectional, primarily qualitative data collected in four rural districts in Zambia, we aimed to explore community perceptions of COVID-19 disease and vaccines, including perceived motivators, cues to action, benefits, and barriers to vaccine uptake as guided by the Health Belief Model. In-depth interviews (IDIs) were conducted in late 2021 with women of reproductive age who were enrolled in an early childhood development study. Although two-thirds of the 106 respondents reported low perceived risk of catching COVID-19, they expressed concern that the COVID-19 pandemic had impacted their daily lives and feared effects of the disease. They had generally positive beliefs that the vaccine would be accepted among their communities when it became more widely available. Reported motivators to vaccine uptake included desire for protection against COVID-19 and understanding vaccine purpose, due to ongoing education from health personnel, neighbors, friends, radio, and church leaders. Misinformation or reported bad experiences served as cues away from vaccine uptake. Examples of misinformation included the vaccine causing COVID-19 or another disease and death and vaccines being associated with the devil and against Christian beliefs. Accounts of pain after receiving the vaccine also discouraged uptake. Perceived benefits included a desire to be protected from the disease, belief in the effectiveness of the vaccine, fear of catching COVID-19, and belief the vaccine would limit negative effects. Health system implementers and policy makers should consider recipient motivators and cues to action to further increase vaccination rates.

Political and Community Logics of Emergent Disease Vaccine Deployment: Anthropological Insights from DRC, Uganda and Tanzania

With a growing number of emerging infectious diseases and the rapid development of vaccines during epidemics and pandemics, public health officials at the global and national level have reported concerns about vaccine hesitancy, often attributing this to a problem of misinformation and poor understanding of risk. However, social scientists have found that vaccination perceptions are complex and multi-faceted. By focusing on the historical, cultural and political influences that affect vaccine acceptance, as well as social justice questions that examine the fair distribution of vaccines, we explore the political and community logics of vaccine deployment using a case study approach. We found differing logics depending on the vaccine and the context and argue that political and community logics come to the forefront during outbreaks as vaccine strategies often are imposed—in different ways—by the Global North. We suggest that, prior to the development and deployment of new vaccines for emergent diseases in the Global South, political level and community logics must be acknowledged and engaged with.

Impact of Different Foot and Mouth Disease Vaccine Schemes in Cross-Neutralization Against Heterologous Serotype O Strains in Cattle.

The high antigenic variability of the foot-and-mouth disease virus (FMDV) represents a challenge for developing prophylactic strategies, stressing the need for research into vaccines offering broad protection against a range of virus strains. Here, the heterotypic cross-reaction using different vaccine schemes against serotype O strains was studied, evaluating the impact of revaccination, antigen dose, and incorporation of additional FMDV serotypes. Naïve cattle were immunized with seven distinct FMDV vaccines, receiving three doses of the same formulation at 0, 28, and 56 days post-primary vaccination (dpv). Serum samples were collected up to 70 dpv and tested by a virus-neutralizing test against serotype O strains from a South American lineage and two strains representative of two Asian lineages. Our results showed that vaccines containing the ME-SA topotype O1/Campos strain developed cross-neutralizing responses against the two Asian viruses after the first vaccination. In contrast, significant heterotypic neutralizing antibody titers against the homologous topotype strain were only found after the second vaccination, indicating that the phylogenic relationship may differ from the antigenic profiles for these two viruses. The amount of the O1/Campos strain and the revaccination were essential factors for neutralization against the homologous- and heterologous-type O FMDV viruses. The strain composition of the vaccine was only relevant for cross-neutralization against one of the Asian strains, suggesting potential intra-serotypic divergences for this pattern.

Behavioural economics to improve and motivate vaccination in primary care using nudges through the electronic health record: rationale and design of the BE IMMUNE randomised clinical trial

IntroductionAnnual influenza vaccination reduces disease burden but vaccination rates are suboptimal, with persistent disparities among subpopulations. The purpose of this trial is to evaluate multicomponent behavioural economic nudge interventions to clinicians and patients to increase influenza vaccination. This trial also includes an intensification nudge to reduce disparities in vaccination among older adult, primary care patients.MethodsThis is a two-part, multisite cluster randomised, pragmatic clinical trial. In the first part, a multicomponent nudge intervention will be tested over approximately 6 months (September 2023–February 2024). The second part consists of a replication trial conducted at an additional site during the following influenza season (September 2024–February 2025). Primary care clinics will be randomised to the nudge intervention or usual care. Eligible clinicians and patients at intervention clinics will receive the intervention, and patients deemed high risk for not receiving a vaccine will be further randomised to receive an intensification nudge. The primary outcome is vaccine completion during the eligible visit and the secondary outcome is vaccine completion within 3 months of the eligible visit.AnalysisThe effect of the clinic-level nudge intervention on the primary and secondary outcomes will be evaluated using generalised estimating equations (GEEs) with a clinic-level exchangeable working correlation to account for clustering of observations within the clinic. GEE models with an independent working correlation will be used to evaluate the impact of the additional intensification nudge on the primary and secondary outcomes.Ethics and disseminationThe University of Pennsylvania Institutional Review Board (IRB) approved this trial and serves as the single IRB of record (IRB #851838). Results will be disseminated via peer-reviewed publication and conference presentations.Trial registration numberNCT06057727.

Development and Evaluation of a Novel Chimeric Genotype VII Newcastle Disease Vaccine: Overcoming Maternal Antibody Interference and Spray Administration.

Newcastle disease virus (NDV) poses a significant threat to the poultry industry, with the emergence of genotype VII NDV leading to extensive outbreaks and economic losses. Vaccination is the primary means of controlling NDV, but the presence of maternal antibodies (MDAs) can interfere with the immunological effect of live virus vaccines. Thus, we constructed a chimeric NDV live virus vaccine, LX-OAI4S, by replacing the extracellular regions of the F and HN genes of the NDV LX strain with the corresponding regions of the A-VII vaccine strain. The chimeric vaccine LX-OAI4S demonstrated high genetic stability, good safety, and strong reproductive capacity in chicken embryos. The LX-OAI4S vaccine induced rapid antibody production in specific pathogen-free (SPF) and commercial chickens via the intranasal and intraocular (IN/IO) routes, with hemagglutination inhibition (HI) antibody titers reaching 4.71 ± 1.03 log2 at 7 days post-vaccination (dpv), significantly higher than those of the two classical vaccine strains La Sota and VG/GA. The LX-OAI4S vaccine group provided effective protection against the challenge of genotype VII NDV virulent strain JS2/06 and inhibited viral shedding. When administered via spray, the LX-OAI4S vaccine elicited high systemic immunity against NDV in both SPF and commercial chickens, effectively protecting against clinical disease and reducing viral shedding. The chickens were exposed to high-dose vaccine for spray vaccination, and no adverse reactions were observed after vaccination. Despite the presence of anti-NDV MDAs in chickens, the NDV-specific antibody titers were significantly greater in the vaccinated groups than in the unvaccinated group. The vaccine exhibited high immunogenicity and the potential to overcome maternal antibody interference. The LX-OAI4S vaccine is a promising candidate for an ND vaccine. Its administration via spray can effectively prevent the occurrence of ND, making it a valuable tool for the poultry industry.

Battling Kyasanur forest disease: the race for robust and long-lasting Kyasanur forest disease vaccine

Battling Kyasanur forest disease: the race for robust and long-lasting Kyasanur forest disease vaccine

Developer and Partnership Differences in COVID-19 and Other Infections: Insights from DNA Vaccines.

Historically, vaccine development has been heavily supported by government and public institutions. On the other hand, private biopharmaceutical companies have played a significant role in the development of innovative new therapies using novel pharmaceutical technologies. COVID-19 vaccines using new vaccine technologies, such as mRNA and adenoviral vectors, were rapidly developed by emerging biopharmaceutical companies in collaboration with large corporations and public organizations. This underscores the crucial role of emerging biopharma and public-private partnerships in advancing new vaccine technologies. While these innovations have been suggested as models for future vaccines, their applicability to other infectious diseases requires careful assessment. This study investigated the characteristics of the developers and partnerships in the development of DNA vaccines as a next-generation vaccine platform. The analysis revealed that while emerging biopharmaceutical companies and private-private and private-public partnerships were crucial during the COVID-19 pandemic, public organizations and public-public collaborations primarily led to the clinical development of vaccines for other diseases. Strategies for vaccine development using new vaccine technologies should be tailored to the specific characteristics of each disease.

Virus-like Particles-Based Vaccine to Combat Neurodegenerative Diseases.

Neurodegenerative diseases are regarded as gradual, incurable conditions with an insidious onset. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most prevalent neurodegenerative diseases reported globally. Developing effective treatment strategies for neurodegenerative diseases has remained a primary objective and a huge challenge for researchers. The therapeutic medications that are now approved for the treatment of neurodegenerative diseases merely treat the symptoms; the underlying pathology is not addressed. Therefore, the emergence of novel disease-modifying therapeutic modalities such as immunotherapy has opened a new path in developing effective treatments for neurogenerative diseases. Compared to other types of subunit active vaccines, virus-like particles (VLPs) are considerably more immunogenic as they present dense and repetitive viral antigen epitopes on their surface, which can trigger both humoral and cell-mediated immune responses. They are also a much safer option than the traditional inactivated and live-attenuated vaccines since they are devoid of viral genomes and are, therefore, non-pathogenic and non-infectious. Researchers have turned their attention to VLPs as an active immunotherapy candidate for AD due to the lessons learned from the AN1792 trial. Studies have shown that they effectively induce anti-Aβ, anti-tau, and anti-α-Synuclein antibodies while avoiding T-cell-related immune reactions in animal models of AD and PD. This review compiles the findings of preclinical animal model studies and clinical investigations on VLP-based vaccines for neurogenerative diseases thus far. The technical limitations and potential difficulties associated with the future application of VLP-based vaccines in patients with neurodegenerative diseases have also been covered.

Association of Major Histocompatibility Complex Polymorphism With Acute Phase Response in Broiler Chicken.

Stress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli. This study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens. The allelic diversity of the LEI0258 microsatellite marker was determined in 120 Ross broilers. In addition, acute phase proteins (APPs), including serum amyloid A (SAA) and alpha-1-acid glycoprotein (AGP), were analysed as markers of the APR. Furthermore, leukocyte count and the heterophil/lymphocyte ratio (H/L ratio) were examined. The antibody response to the Newcastle disease vaccine (NDV) was also measured to assess humoral mediated immunity. Lastly, the correlation between immune responses and MHC alleles was investigated to identify the most effective alleles in a stress-related situation. A total of six alleles, ranging from 195 to 448bp, were identified. Association study revealed a significant influence of MHC alleles on APPs in Ross population (p<0.05). Notably, Allele 448 had a significant correlation with SAA concentration and the H/L ratio. Allele 207 displayed a positive association with AGP concentration, whereas Allele 195 showed a negative association. Furthermore, a significant association was observed between Allele 448 and basopenia, as well as between Allele 195 and monocytosis. Results confirmed the significance of MHC as a candidate gene marker for immune responses, which supports its use for vaccine design, genetic improvement of disease-resistant traits and resource conservation in commercial broiler chickens.