Specific Vaccine Research Articles

Pasteurella multocida and Mannheimia haemolytica; virulence factors, diseases, and notably increasing antibiotic resistance rate among their isolates: a comprehensive review

TThe current review on Pasteurella multocida and Mannheimia haemolytica tried to shed light on these two organisms due to their medical and economic importance as well as to their elevating antibiotic resistance rate among the isolates from animals basically cattle, sheep, and goats. In this comprehensive review, we screened both old and recently published works that are available electronically on authorized scientific sites. Here we provide the latest data on those organisms their structure, suitable growth conditions, virulence factors, pathogenesis, their associated diseases, and their distribution along with antibiotic resistance emergence and the possibility of more new emergences of resistant isolates among species of both organisms. Lastly, we reviewed all the old and modern methods for diagnosis, controlling, and preventing the occurrence of diseases caused by these organisms besides studying and reviewing the effective ways to manage antibiotic resistance issues. Our review concluded that more specific research is needed to shed light on phenotype and genotype differences among those organisms, some issues should be subjected to intensive investigations and research focus such as emerging and re-emerging infectious diseases caused by these organisms and antigenic variants between agents. Evaluation of innate and adaptive immunity after infections or vaccinations is important for producing more specific drugs or vaccines in the future.

Evaluating the impact of school-based influenza vaccination programme on absenteeism and outbreaks at schools in Hong Kong: a retrospective cohort study protocol

IntroductionSeasonal influenza causes annual school breaks and student absenteeism in Hong Kong schools and kindergartens. This proposal aims to conduct a retrospective cohort study to evaluate the impact of a school-based influenza vaccination (SIV) programme on absenteeism and outbreaks at schools in Hong Kong.MethodsThe study will compare schools that implemented the SIV programme with schools that did not. The data will be sourced from school records, encompassing absenteeism records, outbreak reports, and vaccination rates. We will recruit 1000 students from 381 schools and kindergartens in 18 districts of Hong Kong starting June 2024. The primary outcome measures will include absenteeism rates due to influenza and school influenza outbreaks. Secondary outcomes will consist of vaccination coverage rates and the impact of the SIV programme on hospitalisations due to influenza-like illness. A t-test will be conducted to compare the outcomes between schools with and without the SIV programme.Ethics and disseminationThe school completed signing the participants’ informed consent form before reporting the data to us. Our study has been approved by the Hospital Authority Hong Kong West Cluster IRB Committee (IRB No: UW 17–111) and was a subtopic of the research “The estimated age-group specific influenza vaccine coverage rates in Hong Kong and the impact of the school outreach vaccination program”.Trial registrationThis study will be retrospectively registered.

Long-term complications of COVID-19 in Jordan: A study on persisting symptoms and management

BackgroundThe COVID-19 pandemic has led to the emergence of a significant health issue – post-COVID-19 syndrome (PCS), characterized by long-term complications in survivors. This study focused on Jordan to assess the prevalence of PCS, associated symptoms, and potential influencing factors, including vaccine types. MethodsA cross-sectional study recruited 500 participants from various regions in Jordan. Structured questionnaires were used to collect data on participant demographics, symptoms, and treatment approaches. The study also investigated the relationship between specific symptoms and different COVID-19 vaccines. ResultsThe majority of participants were aged 25–55 years, well-educated, and had chronic comorbidities. Notable sensory complications included anosmia and dysgeusia, while psychiatric symptoms and reduced sexual desire were also prevalent. Interestingly, Pfizer® and Sinopharm® vaccines were linked to distinct symptom patterns. Participants pursued various treatments, including pharmacological and non-pharmacological options such as honey and vitamins. Relatives, friends, and pharmacists were the primary sources of information for participants. ConclusionThe study underscores the significant burden of PCS in Jordan and highlights the necessity for tailored interventions, mental health support, and effective communication strategies in post-COVID-19 care. The findings contribute to a comprehensive understanding of PCS and offer valuable guidance for healthcare systems in addressing the evolving healthcare needs of COVID-19 survivors.

Exploring the Communication, Information, and Education Strategies of the Indonesian FDA for COVID-19 Vaccine Development

The COVID-19 pandemic has become a complicated problem faced by the world. The absence of specific antiviral drugs or vaccines at the beginning of the outbreak made the public health approach the primary strategy for preventing the spread of COVID-19. The lack of transparency at the start of the COVID-19 outbreak also led to public misinformation. WHO called it an infodemic, an excess of information, whether true or not, making it difficult for people to determine valid references. In Indonesia, misinformation on health matters is not a new difficulty and is in the top rank along with socio-political. The government utilizes social media to provide information to the citizens. Social media itself has a vital role in the infodemic as a medium for disseminating information, whether credible or not. The Indonesian FDA plays an essential role in conducting education through social media. This study aims to map the elements forming citizens' engagement in Indonesian FDA social media use, especially in disseminating information about the COVID-19 vaccine. This study uses a regression method with citizens' engagement (calculated from the number of likes and comments) as the dependent variable. Three independent variables form citizen engagement elements: media richness, content production, and content type defined by the government. The sentiment toward government Instagram posts was measured by analyzing citizens' comments using the dataset from InSet Semantic Lexicon. Based on negative binomial regression results, data obtained that the framework developed in this research was statistically significant in observing the phenomenon. Media richness and content production significantly affect citizens' engagement. On the other hand, original and informative content encourages more citizen engagement. Generally, public sentiment on Indonesian FDA Instagram content, both head office and regional offices, tends to be more positive than negative.

The pathogenicity and potential risk evaluation of Zika virus to cause mysterious "Disease X": A brief report.

Disease X is included to represent an unknown pathogen that has the potential to spread globally and trigger significant epidemics. The World Health Organization (WHO) and the Global Alliance for Vaccine and Immunization (GAVI) recommend 10 potential disease organisms responsible for disease X. Among them, the Zika virus (ZIKV) is one of the potential organisms. The present work aimed to evaluate the current pathogenicity and potential risk of the ZIKV for public health emergencies. We performed a brief review of existing literature from available sources using Zika fever, Zika virus, and Flaviviridae as keywords and extracted relevant information for this review. The primary way that the ZIKV transmits to humans is by mosquito bites (Aedes aegypti and Aedes albopictus). Typically, Aedes mosquitoes bite during the day. As an RNA virus, the ZIKV is well-known for its rapid mutation rate. ZIKV strains or variations can arise due to genomic mutations, and they occur through various processes, including replication errors, recombination, and selection pressure. Nowadays, the ZIKV has also evolved into a global pandemic because the four-amino acid sequence fits the envelope protein's 154 glycosylation motif, which may be involved in virulence. There is no specific medicine or vaccine available for the prevention or treatment of ZIKV infection. Therefore, personal protective measures should be the way to prevent ZIKV disease. Therefore, avoiding exposure is the best way to prevent problems from ZIKV to mosquitoes.

Protective Efficacy of Lyophilized Vesicular Stomatitis Virus-Based Vaccines in Animal Model.

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus-based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus-based vaccines will each require extensive analysis to optimize stabilizing formulations.

Exploring pre-pandemic patterns of vaccine decision-making with the 5C model: results from representative surveys in 2016 and 2018.

The 5C psychological antecedents of vaccination (Confidence, Complacency, Constraints, Calculation, and Collective Responsibility) facilitate understanding vaccination decisions in specific target groups as well as the general public's informational needs. This study aims to explain pre-pandemic vaccination behaviour (a) in general, (b) for specific vaccines such as influenza, and (c) for certain target groups (e.g. people over the age of 59years, parents, healthcare workers), using the 5C model and sociodemographic variables. The intention to get an influenza vaccination was also analysed for target groups. The 5C, self-reported vaccination behaviour and the intention to vaccinate were collected in two representative telephone surveys in Germany - one in 2016 (n1 = 5,012) and another in 2018 (n2 = 5,054). Parents, people over the age of 59years, chronically ill people, people with a migratory background, pregnant women and healthcare workers were target groups. Overall, the 5C model had higher explanatory power than sociodemographic variables. The pattern of vaccine hesitancy slightly differed between vaccinations and target groups. Confidence in safety and effectiveness was always a significant predictor. Complacency (the underestimation of disease risks) and Constraints were significant predictors as well. Calculation (of risks and benefits) was important for influenza vaccination intentions. This work builds an important benchmark for understanding potential changes in vaccine acceptance due to the pandemic. The benchmark can be used in research on potential effects of the pandemic on vaccination behaviours. Intervention designers can also use the results to understand specific audiences and their vaccination decisions.

Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice

Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as Tcell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines. Our study provides a favorable approach for developing MPXV-specific vaccines by using a circular mRNA platform and opens up novel avenues for future vaccine research.

Antiviral Activity of Flavonoids from Bauhinia holophylla Leaves against Zika virus

Zika virus (ZIKV) is involved in the etiology of serious nervous system pathologies. Currently, there are no specific and effective vaccines or antiviral drugs to prevent the diseases caused by ZIKV. This study aimed to assess the activity of flavonoids present in crude hydroethanolic extract (CHE) and fractions obtained from B. holophylla leaves against ZIKV. O-glycosylated flavonoids were characterized by high-performance liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS). The cytotoxic concentration and the effective concentration for 50% of the cells (CC50 and EC50, respectively) were determined, and the selectivity index (SI) was calculated. Molecular networks were constructed based on the chemical composition of the samples and global antiviral activity data using the Global Natural Products Social Molecular Networking (GNPS) platform. Protein–ligand docking was performed in the NS2B-NS3 protease, NS3 helicase, and NS5 methyltransferase of the ZIKV. CHE showed greater antiviral activity at a multiplicity of infection (MOI) of 1.0, with an EC50 of 11.93 µg/mL, SI = 13.38, and reduced cytopathic effects. Molecular networks indicated that O-glycosylated flavonoids are responsible for the activity against ZIKV, being quercetin-O-deoxyhexoside more selective and effective. Molecular docking confirmed the inhibitory activity of quercetin-O-deoxyhexoside, which showed an affinity for the tested targets, especially for NS2B-NS3 protease. The results showed that B. holophylla has flavonoids with potential for future therapeutic applications against ZIKV.

Activation of the NLRP3 inflammasome by human adenovirus type 7 L4 100-kilodalton protein.

Human adenovirus type 7 (HAdV-7) is a significant viral pathogen that causes respiratory infections in children. Currently, there are no specific antiviral drugs or vaccines for children targeting HAdV-7, and the mechanisms of its pathogenesis remain unclear. The NLRP3 inflammasome-driven inflammatory cascade plays a crucial role in the host's antiviral immunity. Our previous study demonstrated that HAdV-7 infection activates the NLRP3 inflammasome. Building upon this finding, our current study has identified the L4 100 kDa protein encoded by HAdV-7 as the primary viral component responsible for NLRP3 inflammasome activation. By utilizing techniques such as co-immunoprecipitation, we have confirmed that the 100 kDa protein interacts with the NLRP3 protein and facilitates the assembly of the NLRP3 inflammasome by binding specifically to the NACHT and LRR domains of NLRP3. These insights offer a deeper understanding of HAdV-7 pathogenesis and contribute to the development of novel antiviral therapies.

Attitudes regarding vaccination on the example of COVID-19 prevention.

COVID-19 vaccines for public use were approved at the turn of 2020 and 2021. The level of vaccination coverage against COVID-19 in Poland is one of the lowest in Europe. Despite scientific studies there are people who are afraid of vaccinations and spread false information about them. Vaccinations against COVID-19 allowed to learn about the attitudes of people who decided to be vaccinated, which can be used to improve the effectiveness of the infectious diseases prevention in the work and public environment. The aim of the study was to analyze the main reasons determining a decision to get vaccinated against COVID-19. The study was carried on among all the people who decided to be vaccinated against COVID-19 in Nofer Institute of Occupational Medicine in Łódź. All vaccinated people completed an anonymous survey containing questions related to the most important factors, which encouraged them to undergo this vaccination. The study involved 945 people vaccinated against COVID-19. Statistical significance was revealed between 3 different reasons (one's own health, stress-free work, safe travelling and easier access to entertainment) for getting vaccinated and age, gender and a form of employment. The authors also found statistical significance of the correlation between the age, gender, education and form of employment of the respondents and the reason for choosing the specific vaccine product. Despite evidence presented by scientists about the effectiveness and safety of vaccinations, many people refused and still refuse to receive the vaccine. In order to increase the readiness of the population for vaccinations against COVID-19 and subsequent ones, if there is a need to limit new epidemics, the following should be done: introduce activities to raise health awareness, intensify strategies and campaigns aimed at increasing public trust in available vaccines against COVID-19, devolop individualized messages that contribute to vaccine hesitancy. Med Pr Work Health Saf. 2024;75(2):123-131.

Antibody response to malaria vaccine candidates in pregnant women with Plasmodium falciparum and Schistosoma haematobium infections.

Malaria in pregnancy has severe consequences for the mother and foetus. Antibody response to specific malaria vaccine candidates (MVC) has been associated with a decreased risk of clinical malaria and its outcomes. We studied Plasmodium falciparum (Pf) and Schistosoma haematobium (Sh) infections and factors that could influence antibody responses to MVC in pregnant women. A total of 337 pregnant women receiving antenatal care (ANC) and 139 for delivery participated in this study. Pf infection was detected by qPCR and Sh infection using urine filtration method. Antibody levels against CSP, AMA-1, GLURP-R0, VAR2CSA and Pfs48/45 MVC were quantified by ELISA. Multivariable linear regression models identified factors associated with the modulation of antibody responses. The prevalence of Pf and Sh infections was 27% and 4% at ANC and 7% and 4% at delivery. Pf infection, residing in Adidome and multigravidae were positively associated with specific IgG response to CSP, AMA-1, GLURP-R0 and VAR2CSA. ITN use and IPTp were negatively associated with specific IgG response to GLURP-R0 and Pfs48/45. There was no association between Sh infection and antibody response to MVC at ANC or delivery. Pf infections in pregnant women were positively associated with antibody response to CSP, GLURP-R0 and AMA-1. Antibody response to GLURP-R0 and Pfs48/45 was low for IPTp and ITN users. This could indicate a lower exposure to Pf infection and low malaria prevalence observed at delivery.

Recent advances on vaccines against malaria: A review

This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines. Data on malaria vaccine development was collected through a comprehensive review. The literature search was performed using databases including Google Scholar, PubMed, NIH, and Web of Science. Various novel approaches of vaccination are being developed, including those based on radiation-attenuated strategies, monoclonal antibodies, targeted immunogenic peptides, RNA and DNA vaccines, nanoparticle-based vaccines, protein-based vaccination protocols, and whole organism-based vaccination strategies. Trials on RTS, S have entered phase III testing, and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials. Mathematical modeling, combined drug and vaccine strategies, mass drug administration, polyvalent vaccine formulations, and targeted vaccination campaigns is playing an important role in malarial prevention. Furthermore, assessing coverage, accessibility, acceptability, deployment, compilation, and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.

Central nervous system infections in the tropics.

Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.

Immune Specific and Tumor-Dependent mRNA Vaccines for Cancer Immunotherapy: Reprogramming Clinical Translation into Tumor Editing Therapy.

Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice for future cancer immunotherapy. Ideal personalized tumor-dependent mRNA vaccines could stimulate both humoral and cellular immunity by overcoming cancer-induced immune suppression and tumor relapse. The stability, structure, and distribution strategies of mRNA-based vaccines have been improved by technological innovations, and patients with diverse tumor types are now being enrolled in numerous clinical trials investigating mRNA vaccine therapy. Despite the fact that therapeutic mRNA-based cancer vaccines have not yet received clinical approval, early clinical trials with mRNA vaccines as monotherapy and in conjunction with checkpoint inhibitors have shown promising results. In this review, we analyze the most recent clinical developments in mRNA-based cancer vaccines and discuss the optimal platforms for the creation of mRNA vaccines. We also discuss the development of the cancer vaccines' clinical research, paying particular attention to their clinical use and therapeutic efficacy, which could facilitate the design of mRNA-based vaccines in the near future.

Abstract 6336: Unleashing CAR T cell activity against osteosarcoma using tumor specific RNA-based vaccination

Abstract Background: Metastatic osteosarcoma (OSA) has a dismal prognosis despite novel targeted therapies, including CAR T cells. Unleashing CAR T cell therapy against poorly immunogenic cancers requires new technologies that activate the tumor microenvironment (TME), while inducing CAR T cell migration, proliferation, and persistence into tumor to sustain tumor-specific immunity. We have developed tumor RNA-loaded nanoparticle (CD70-encoding RNA-NP) vaccines to overcome CD70-specific CAR T cell limitations in OSA. Methods: Using two murine solid tumor models (K7M2 osteosarcoma and B16F0 melanoma, in Balb/c and C57Bl/6 background) highly metastatic to lungs, we implant K7M2 and B16F0 intravenously (i.v.). We subsequently generated NPs complexed with RNA encoding for CD70 antigen and control vaccine (GFP RNA). RNA-NPs are administered intravenously beginning on day 5 post-tumor implantation and day 7, 14 & 21. Mouse CD70-specific CAR T cells are manufactured after activation of T cells with CD3 and CD28 antibodies for 2 days. CAR T cells are ready for use in downstream experiments 2 days after pMSGV8-mCAR transduction and cells were injected (i.v.) on day 6. Results: In preliminary data, we show that intravenous administration of CD70-encoding RNA-NPs rapidly recruit CD70-directed CAR T cells into tumor stroma unlocking their activity in two immunocompetent aggressive lung metastatic tumor models. Interestingly, regression of CD70-expressing tumors associates with CAR T cell mobilization out of peripheral blood and into reticuloendothelial (RES) tissues (i.e., lung, and spleen), a phenomenon that correlates with upregulation of vaccine-induced type I interferon (IFN) and activation of CCR2 pathway. In addition to the CAR T-mediated antitumor killing, an antigen spreading phenomenon was observed. The long-term survival benefit (150 days) provided by this approach reached 70-80% in both models compared with 0-10% of control groups. Conclusions: Based on these findings, we hypothesize that tumor trafficking and persistence of CD70 CAR T cells depend on coordinated cytokine/chemokine signaling that can be ignited through intravenous RNA-NP vaccination. RNA-NPs in combination with CAR T cells prolong long-term survival of mice bearing these aggressive tumor models which was not only mediated by CAR T cells but also by activation of endogenous adaptive immunity. Future studies include the evaluation of this approach in large animal models prior to translation into first-in-human clinical trials. Citation Format: Arnav Barpujari, Rui Liu, Elizabeth Ogando-Rivas, Xiaojie Ma, Haipeng Taoa, Hector Gomez, Duane Mitchell, Jianping Huang, Elias Sayour, Paul Castillo. Unleashing CAR T cell activity against osteosarcoma using tumor specific RNA-based vaccination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6336.

Abstract 4804: Prevalence of anal HPV infection in women attending a gynecology and colposcopy clinic: Assessing the potential impact of HPV vaccination

Abstract Human papillomavirus (HPV) accounts for over 80% of anal cancer cases. In the effort to prevent HPV-related cancers, the 9-valent HPV vaccine emerged as a crucial intervention, targeting HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the previous 4-valent (types 6,11,16,18) and 2-valent (types 16, 18). This study involved 213 women aged 21-50 attending gynecology and colonoscopy clinics in San Juan, Puerto Rico. The study assessed anal HPV prevalence and analyzed vaccination status-related differences. Anal swabs were collected for HPV testing using the ATILA AmpFire, targeting 17 HPV types. This method identified 15 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68) and two low-risk HPV types (6 and 11). Prevalence of any HPV, HR-HPV, and LR-HPV, and of specific HPV types were calculated by overall and vaccination status. Differences were assessed for statistical significance (p<0.05) using Fisher's exact or Pearson χ2 test. The mean age of women was 36.0 ± 5.9 years. Overall, 19.7% (n=44) had received the HPV vaccine; among them, 52.2% (n=23) had received the 4-valent vaccine, 2.3% had received the 2-valent vaccine, 2.3% had received the 9-valent vaccine, and 43.2% were uncertain about their specific HPV vaccine type. The prevalence of anal HPV infection was 68.5% for any HPV, 61.5% for HR-HPV, and 15.0% for LR-HPV. The most prevalent HR-HPV types were HPV 56 (13.2%), HPV 68 (11.7%), and HPV 66 (11.2%). There were no statistically significant differences in the prevalence of any HPV, HR-HPV, and LR-HPV between vaccinated and unvaccinated women. The most common HR-HPV type among vaccinated were HPV 66 (20.5%), HPV 31 (18.2%), HPV 56 (15.9%), while the most common among unvaccinated women were HPV 56 (12.4%), HPV 68 (12.4%), and HPV 16 (12.4%). Additionally, when evaluating as a grouped variable, the HPV genotypes covered by the 4-valent, unvaccinated women had a significantly higher prevalence of these types as compared to those vaccinated (28.9% vs. 13.6%, respectively, p-value =.03). The unvaccinated women showed a lower prevalence for HPV types covered by the 9-valent vaccine compared to the vaccinated cohort (43.2% vs. 45.5%). However, this difference was not statistically significant. We found a high prevalence of anal HPV among these women, with lower prevalence of 4-valent and 2-valent HPV types among vaccinated women, evidencing the pivotal role of HPV vaccination. Future research should assess the 9-valent vaccine's long-term effectiveness against more HPV types. Funding: Research Centers in Minority Institutions (RCMI), University of Puerto Rico (NIMHD # 2U54MD007600-36), and CAPAC Research Training Program (NCI #R25CA240120). Citation Format: Anelisse Dominicci-Maura, Ana Patricia Ortiz, Josefina Romaguera, Filipa Godoy-Vitorino. Prevalence of anal HPV infection in women attending a gynecology and colposcopy clinic: Assessing the potential impact of HPV vaccination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4804.

Abstract 4102: Treatment with androgen receptor targeting vaccines provides an overall survival benefit in AR-V7 expressing tumor models

Abstract Background: Androgen receptor (AR) signaling inhibition is part of the mechanism behind many effective prostate cancer therapies, including androgen deprivation and next generation anti-androgens. However in castration resistant prostate cancer up to 50% of treatment resistance has been linked to AR amplification or expression of the constitutively active RNA splice variant, AR-V7. Although the use of immune checkpoint blockade has failed to demonstrate clinical success, immunotherapeutic interventions remain attractive as prostate cancer’s relatively slow progression provides time for anti-tumor immune responses to develop. Cancer specific vaccines have the potential to enable and enhance tumor specific immune responses by stimulating and directing T cell immunity to important oncologic targets. We hypothesized that a cancer vaccine designed to induce a T cell response against cells expressing high levels of AR would result in an anti-tumor effect and potentially prevent or delay the development of therapeutic resistance. Methods: Adenoviral vaccines against AR (Ad-AR) or AR splice variant 7 (Ad-AR-V7) were used to evaluate the potential of AR targeting vaccination in mouse models. We evaluated AR and AR variant specific adaptive responses produced by our vaccines with naïve and tumor-bearing mice by ex vivo peptide restimulation. We challenged vaccinated mice with multiple syngeneic subcutaneous tumor models that we engineered to express AR-V7, including a PTEN-/- p53-/- prostate tumor cell line. Finally we tested our vaccines in a therapeutic regimen, vaccinating mice after implanting our subcutaneous AR-V7 expressing models. Results: Across multiple strains of mice, AR or AR-V7 targeting adenoviral vaccination induced robust adaptive immune responses against the N-terminal domain of AR. Vaccination with either Ad-AR or Ad-AR-V7 resulted in significant anti-tumor responses, providing a significant overall survival benefit and complete tumor rejection by the majority of mice vaccinated against AR or AR-V7. Similarly tumor bearing mice treated with Ad-AR or Ad-AR-V7 vaccination displayed tumor growth inhibition or complete tumor regression resulting in an overall survival benefit. Additionally, we found that vaccine responses were unaffected by the use of the approved antiandrogen drug enzalutamide, suggesting that vaccinations could be deployed in tandem with standard-of-care therapies. Conclusions: Vaccination against AR and AR splice variants can induce AR specific adaptive immune responses capable of inhibiting the growth of AR-V7 expressing tumor models, illustrating the potential of AR and its splice variants as immunologic targets in prostate cancer. Citation Format: Robert D. Marek, Junping Wei, Tao Wang, Xiao-Yi Yang, Gangjun Lei, Zachary C. Hartman. Treatment with androgen receptor targeting vaccines provides an overall survival benefit in AR-V7 expressing tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4102.

The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination

Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and Tcells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1β (IL-1β), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57+ NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57+ NK subset was particularly prominent in malesand in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G).

Differences in social media use by COVID-19 vaccination status

The near-ubiquitous use of social media in the United States (U.S.) highlights the utility of social media for encouraging vaccination. Vaccination campaigns have used social media to reach audiences, yet research linking the use of specific social media platforms and vaccination uptake is nascent. This descriptive study assesses differences in social media use by COVID-19 vaccination status among adults overall and those who reported baseline vaccine hesitancy. We used data from a nationally representative longitudinal survey of U.S. adults administered between January 2021–August 2022 (n = 2,908). Results indicated a positive association between frequent Instagram and/or Twitter use and vaccination status (p <.05). Among baseline vaccine hesitant adults, results indicated a positive association between frequent TikTok, Instagram, and/or Twitter use and vaccination status (p <.05). Findings have implications for research that examines the content of social media platforms and their environment on vaccine attitudes and uptake.