Vaccine Efficacy Research Articles

Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development

AbstractRTS,S and R21 are the only vaccines recommended by the WHO to protect children from Plasmodium falciparum (Pf) clinical malaria. Both vaccines target the Pf sporozoite surface protein circumsporozoite protein (CSP). Recent studies showed that human antibodies neutralize Pf sporozoites most efficiently when simultaneously binding to the PfCSP NANP repeat and the NPDP junction domain. However, neither RTS,S nor R21 targets this junction domain. To test the potential of the NPDP junction domain and other sites of PfCSP as innovative vaccine targets, we developed multiple vaccine candidates based on cucumber mosaic virus-like particles (CuMVTT-VLPs). These candidates vary in several aspects: the number of targeted NANP repeats, the presence or absence of the junction domain, the cleavage site, and up to three NVDP repeats within the target sequence. Immunogenicity and efficacy studies were conducted in BALB/c mice, utilizing chimeric Plasmodium berghei (Pb) sporozoites, in which the endogenous CSP has been replaced by PfCSP (Pb/PfCSP). We observed a positive association between the number of targeted NANP repeats and the induction of specific IgM/IgG antibodies. Elevated humoral responses led to enhanced protection against parasitemia after Pb/PfCSP sporozoite challenge. Especially high-avidity/affinity antibody formation and vaccine protection were NANP repeat-dependent. Intriguingly, vaccine efficacy was not enhanced by targeting sites on PfCSP other than the NANP repeats. Our data emphasize the dominant role of the NANP repeat region for induction of protective antibodies. Furthermore, we present here novel malaria vaccine candidates with an excellent immunogenic profile that confer sterile protection in mice, even in absence of adjuvants.

IL-7 promotes mRNA vaccine-induced long-term immunity.

Messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, improving the immunogenicity and durability of mRNA vaccines remains a challenge. To elicit optimal immune responses, integrating antigen-encoded mRNA and immunostimulatory adjuvants into a single formulation is a promising approach to enhancing the efficacy of mRNA vaccines. Here, we report an adjuvant strategy to enhance the efficacy of mRNA vaccines by co-loading mRNA encoding the antigen (rabies virus glycoprotein, RABV-G) and mRNA encoding IL-7 into lipid nanoparticles, achieving co-delivery to the same antigen-presenting cells. A single immunization with G&IL-7 mRNA vaccine elicited robust humoral immune responses in mice and conferred complete protection against RABV challenge. Notably, the high levels of neutralizing antibody induced by the G&IL-7 mRNA vaccine were maintained for at least 6months, providing mice with long-term significant and complete protection against RABV. Additionally, IL-7 also enhanced antibody responses against the SARS-CoV-2. These data demonstrate that IL-7 is a potent mRNA vaccine adjuvant that can provide the required immune stimulation in various mRNA vaccine formulations.

Evaluation of rate and severity of COVID-19 infection after vaccination in the age group of 18–25-year population: A questionnaire-based study

Objectives: Covid-19 has been a challenging and challenging pandemic for mankind, with the introduction of the novel coronavirus, SARSCov-2, in late December 2019. Vaccination has proven to be a boon in these challenging times, with the study aiming to determine the efficacy of vaccination against the novel coronavirus in terms of the number of cases affected before and after vaccination and the severity of illness in post-vaccinated Covid-affected individuals. The study aims to learn from the lessons learned during this challenging period. Material and Methods: Students between age group of 18 to 25, from Nashik District, Maharashtra State, India, were the subject of a questionnaire-based study. Using Google Form, a survey was created. Results: It was found that vaccination has reduced the number of positive Covid 19 cases and we have seen a statistically significant decrease in the number of Covid-19-affected individuals. Conclusion: In the present study, we found that the severity is reduced and a smaller number of severe cases are seen after vaccination however the sample was small so this finding was not statically significant.

Global vaccination against hepatitis E virus: position paper from the ESGVH-ESCMID.

Hepatitis E Virus (HEV) is a significant global health issue, impacting both low- and middle-income countries (LMICs) and industrialized nations. HEV genotypes 1 and 2, primarily transmitted through contaminated water, are endemic in LMICs, while genotypes 3 and 4 are zoonotically transmitted in industrialized regions. Acute HEV infection poses severe risks, particularly to pregnant women and immunocompromised individuals, while chronic HEV infection leads to serious complications in those with pre-existing liver disease and transplant recipients. The development of an HEV vaccine offers new prevention opportunities, though its availability and integration into global immunization programs remain limited. This position paper was developed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Viral Hepatitis Study Group (ESGVH) through an extensive review of clinical data, safety profiles, efficacy, and immunogenicity of HEV vaccines. The study group focused particularly on high-risk and special populations, synthesizing global health insights and incorporating recommendations from the Strategic Advisory Group of Experts (SAGE) to formulate strategies for wider HEV vaccination use. The position paper evaluates the efficacy and safety of HEV vaccines in both general and special populations. It identifies key barriers to the integration of HEV vaccines into routine immunization programs, including infrastructure limitations, costs, and vaccine accessibility. The paper also proposes strategies to overcome these challenges and improve vaccine distribution. Furthermore, it addresses ways to enhance public awareness and international cooperation to promote HEV vaccination efforts globally. ESGVH-ESCMID recommends HEV vaccination for high-risk groups, including women of childbearing age, patients with chronic liver diseases, and immunosuppressed individuals. Prioritizing investments in vaccine logistics, integrating diagnostics, and educational outreach can enhance uptake.

DNA tetrahedron nanoparticles service as a help carrier and adjvant of mRNA vaccine.

To investigate the potential of DNA nanoparticles (DNPs) as carriers and adjuvants for mRNA vaccines. Customized oligonucleotides were assembled into DNA tetrahedra (DNA-TH), which were subsequently complexed with streptavidin and mRNA encoding green fluorescent protein (GFP). Various assays were conducted to evaluat the stability of the DNPs, their cellular uptake, immune activation potential, and GFP mRNA transcription efficiency. P53-mutant HSC-3 cells were used to establish a subcutaneous xenograft tumor model to explore the effects of DNPs as carriers and adjuvants in a disease model. The DNPs were remained stable extracellularly and rapidly taken up by antigen-presenting cells. Compared to naked GFP mRNA, DNPs statistically significantly activated immune responses and facilitated GFP mRNA transcription and protein expression both in vitro and in vivo. Immunization with DNP-GFP mRNA complexes induced higher antibody titers compared to naked mRNA. The DNPs demonstrated good biocompatibility. DNP-p53 inhibited the growth of subcutaneous xenograft tumors in mice with p53-mutant HSC-3 cells, outperforming both the naked p53 mRNA and blank control groups, with a statistically significant difference (P < 0.05). DNA nanoparticles show promise for improving mRNA vaccine delivery and efficacy. Further optimization of these nanoparticles could lead to highly effective mRNA vaccine carriers with broad applications.

Mycobacterium tuberculosis Antigen Rv1471 Induces Innate Immune Memory and Adaptive Immunity against Infection.

Protein subunit vaccines form a key pipeline for developing novel tuberculosis (TB) vaccines. Mycobacterium tuberculosis (Mtb) contains approximately 4000 individual proteins. However, only approximately 100 have been evaluated as antigens in the clinical and preclinical stages of vaccine development. Trained immunity-targeting vaccines induce innate immune memory against heterologous infections and enhance antigen-specific adaptive immune responses. However, no trained immunity-targeting subunit TB vaccine has been reported yet. This study tested Rv1471, a thioredoxin secreted by Mtb, as a candidate TB vaccine antigen due to its capacity to stimulate mouse bone marrow-derived macrophages (BMDMs). Rv1471 induced functional and phenotypic maturation of BMDMs in vitro, reflected by the increased production of inflammatory cytokines and surface expression of co-stimulatory molecules. Transcription analysis of Rv1471-trained BMDMs indicated that innate immune memory was activated through pathways of Akt-mTOR-HIF-1α and aerobic glycolysis. Rv1471 also enhanced innate immune memory responses and protection against intracellular infections of different mycobacteria. In a murine model of TB, immunization with Rv1471 formulated with liposomal DDA/MPLA adjuvant produced robust antigen-specific multi-functional CD4+ and CD8+ T-cell immune responses and had substantial protective efficacy against Mtb challenge. Analysis of recall immunity showed that the Rv1471 subunit vaccine triggered robust T-cell immunity post Mtb infection. These findings support the development of an innate immune memory-targeting subunit TB vaccine to increase TB vaccine efficacy.

Rotavirus-specific-IgA and cytokines responses in Ascaris lumbricoides-infected preschool-aged Nigerian children following rotavirus vaccination

ABSTRACT Rotavirus diarrhea and Ascaris lumbricoides (Al) infection increase intestinal morbidity and were associated with altered immune responses that compromise the vaccine efficacy in children. The serum level of rotavirus specific IgA (RV-IgA) and cytokine profiles in A. lumbricoides (AI) infected preschool-aged Nigerian children were estimated following oral rotavirus vaccination. Nineteen of the 149 preschool-aged children (aged 6 to 60 months) with Ascaris lumbricoides infection paired with age and sex-matched helminth – free children were administered with oral rotavirus vaccine after intestinal helminth screening using stool sample concentration technique. Separated sera from 3 mL venous blood samples were collected and estimated for cytokines (IFN–γ, TNF–α, IL-4, IL-8 IL-6, IL-10) and RV-IgA before and three weeks after rotavirus vaccination using Enzyme Linked Immunosorbent Assay. IFN–γ, IL-8, IL-4 were significantly lower at post-vaccination in Al-infected children compared with pre-vaccination. Serum IL-10 was significantly higher at post-vaccination in both Al-infected children and helminth-free controls, compared with pre-vaccination levels (p < 0.05). Pre-vaccination IL-8 and IL-6 were significantly higher in Ascaris lumbricoides–infected children, while the post-vaccination IL-8 was significantly higher in Ascaris lumbricoides–infected compared with control. At post-vaccination period, RV-IgA level was lower in Al-infected children and significantly higher in helminth – free control group compared to pre-vaccination RV-IgA level. Ascaris lumbricoides infection contributed to down-regulation of some cytokines and antibody responses to oral rotavirus vaccine.

A potential platform for future vaccine trials identifies high incidence of symptomatic and asymptomatic influenza infection among children aged 6-23 months in South Africa.

Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both, are important for developing improved vaccines. We estimated influenza infection incidence, and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design. We conducted a prospective cohort study among children aged 6-23 months from May-October 2022. Study nurses collected symptom and temperature data and mid-turbinate nasal swabs twice-weekly irrespective of symptoms; caregivers entered symptom data daily and collected nasal swabs weekly. Samples were tested for influenza using PCR. Of 230 healthy, screened children, 93 were enrolled of whom 87 (94%) completed 6-months follow-up. 95% (4245/4476) of scheduled nurse, 90% (2045/2276) of caregiver swabs, 99% (92/93) of baseline blood collections and 67% (9245/13768) of scheduled symptom diaries were completed. PCR-confirmed influenza incidence was 65% (60/93) for ≥1 infection; 11 (18%) individuals had 2 and 1 (2%) had 3 episodes. Of 73 episodes, 55 (75%) had ≥1 symptom and 37 (51%) had fever (measured and/or reported). Median infection duration was 7 days (interquartile range 4-9). Human RNase P gene was detected in 99% (2032/2045) of caregiver-collected swabs, through which 5 additional episodes were identified. Per episode, caregiver's diaries of reported and measured fever were 19%(25/73,34%) and 11%(15/73,21%) higher than nurse-reported (11/73,15%) and -measured fevers (7/73,10%), respectively. The incidence of influenza infection was high and mainly symptomatic suggesting that this platform could be suitable for future trials of vaccine efficacy and correlates of protection against infection and illness in children.

Abstract B001: CircRNA-derived neoantigen identification in cancer vaccine development

Abstract Immunotherapy has been a popular topic in combating cancer for its great performance in specificity, versatility and durability recently. Cancer vaccines targeting neoantigens have shown clinical efficacy against cancer, eliciting long-lasting immune response and offering a more selective therapeutic approach with less side effects. However, rare mutation rates and low expression levels of neoantigen make it challenging to identify suitable neoantigens. Traditionally, researchers focus on the canonical mRNA transcriptome and proteome to find potential targets. Recent studies suggest that exploring the non-canonical transcriptome and proteome, particularly circular RNAs (circRNAs), can expand the search. CircRNAs, endogenously formed by the unique back-splicing events during pre-RNA processing, can serve as templates for protein synthesis. Some of these non-canonical peptides are specifically expressed in cancer cells, making circRNAs a valid source for neoantigen discovery. We have developed high-throughput circRNA reporter screening methods and mass spectrometry-based peptidomic workflow to pinpoint translating circRNAs and their derived peptides. Using these techniques, we have identified circRNA-derived neoantigens in breast cancer (BC) cell lines that can be used as possible targets for cancer vaccines. These circRNA-derived neoantigens are immunogenic and can trigger dendritic cell (DC) maturation and T cell activation in vitro. Next, we will test these findings by transferring to in vivo mouse system. We will assess cancer vaccine efficacy by targeting the neoantigens using syngeneic mouse tumor models. Our long- term goal is to apply the circRNA neoantigen identification technology to BC patient samples to facilitate cancer vaccine development and improve cancer immunotherapy. Our work will demonstrate the potential of circRNA-derived non canonical neoantigens in cancer vaccines, serving as a crucial first step to prove their effectiveness in therapy. By expanding our search beyond the traditional transcriptome and proteome, we will explore new targets and transform the neoantigen-based treatment. This innovative effort shifts the current understanding of neoantigen sources and opens up new possibilities for targeted cancer therapy strategies. Citation Format: Yi-Cian Zheng, Chun-Kan Chen. CircRNA-derived neoantigen identification in cancer vaccine development [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B001.

GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies.

Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation across individuals in response to vaccination is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification of predictive biomarkers would represent a significant step towards this goal. Moreover, in early phase vaccine clinical trials, small datasets are prevalent, raising the need and challenge of building a robust and explainable prediction model that can reveal heterogeneity in small datasets. We propose a new model named Generative Mixture of Logistic Regression (GeM-LR), which combines characteristics of both a generative and a discriminative model. In addition, we propose a set of model selection strategies to enhance the robustness and interpretability of the model. GeM-LR extends a linear classifier to a non-linear classifier without losing interpretability and empowers the notion of predictive clustering for characterizing data heterogeneity in connection with the outcome variable. We demonstrate the strengths and utility of GeM-LR by applying it to data from several studies. GeM-LR achieves better prediction results than other popular methods while providing interpretations at different levels.

An Optimised Live Attenuated Influenza Vaccine Ferret Efficacy Model Successfully Translates H1N1 Clinical Data

Between 2013 and 2016, the A/H1N1pdm09 component of the live attenuated influenza vaccine (LAIV) produced instances of lower-than-expected vaccine effectiveness. Standard pre-clinical ferret models, using a human-like vaccine dose and focusing on antigenic match to circulating wildtype (wt) strains, were unable to predict these fluctuations. By optimising the vaccine dose and utilising clinically relevant endpoints, we aimed to develop a ferret efficacy model able to reproduce clinical observations. Ferrets were intranasally vaccinated with 4 Log10 FFU/animal (1000-fold reduction compared to clinical dose) of seven historical LAIV formulations with known (19–90%) H1N1 vaccine efficacy or effectiveness (VE). Following homologous H1N1 wt virus challenge, protection was assessed based on primary endpoints of wt virus shedding in the upper respiratory tract and the development of fever. LAIV formulations with high (82–90%) H1N1 VE provided significant protection from wt challenge, while formulations with reduced (19–32%) VE tended not to provide significant protection. The strongest correlation observed was between reduction in wt shedding and VE (R2 = 0.75). Conversely, serum immunogenicity following vaccination was not a reliable indicator of protection (R2 = 0.37). This demonstrated that, by optimisation of the vaccine dose and the use of non-serological, clinically relevant protection endpoints, the ferret model could successfully translate clinical H1N1 LAIV VE data.

Combination application of Pickering emulsion and BLS protein nanoparticles enhances vaccine efficacy.

The deficiency of recombinant protein immune response could be compensated for by using nanoparticle platforms or adding immune enhancers, however existing vaccines or adjuvants struggle to elicit durable cellular immune responses. In this work, a protein nanoscaffold, lumazine synthase isolated from Brucella (BLS) was optimally designed that could facilitate cellular uptake of displayed antigens and the maturation of bone marrow-derived dendritic cells (BMDCs), and enhancing humoral immune responses. To enhance cellular immune response, chitosan hydrochloride-stabilized Pickering emulsion (CHSPE) was evaluated as an adjuvant for the BLS nanoscaffold-based vaccine. CHSPE could enhance the recruitment and activation of DCs at the injection site and the uptake of antigen and activation of DCs in the draining lymph nodes (dLNs), compared with commercial adjuvant ISA 206. In addition, CHSPE induced antigen-specific antibody levels comparable to those of ISA 206 and increased the ratio of central memory T cells (TCM) and effector memory T cells (TEM), and promoted the secretion of Th1-type cytokines. Moreover, CHSPE-formulated vaccine provided a similar level of protection to the live attenuated vaccine and was superior to that of ISA 206. Taken together, the combination of the BLS nanoscaffold and CHSPE provides a feasible strategy for recombinant protein subunit vaccine development.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90th percentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.

Assessing Post-Vaccination Seroprevalence and Enhancing Strategies for Lumpy Skin Disease Vaccination in Korean Cattle

Lumpy skin disease (LSD), caused by the LSD virus (LSDV), a dsDNA virus of the genus Capripoxvirus, represents a significant cross-border infectious threat, particularly impacting cattle and water buffaloes through transmission by blood-feeding insects. Traditionally endemic to Southern Africa, LSD has rapidly spread over the past decade through the Middle East to Eastern Europe and China, reaching Korea in October 2023. This outbreak prompted a nationwide vaccination campaign, addressing both the disease’s severe economic impact and its status as a notifiable disease under the World Organisation for Animal Health. This study assesses the seropositivity of the LSD vaccine in cattle across four Korean provinces 2–3 months post-vaccination, aiming to inform improvements in biosecurity and vaccination strategies. Overall, 30.59% of the cattle tested (1196 out of 3910) exhibited positive antibody responses, comparable to international post-vaccination findings. Analysis further revealed differences in the antibody positivity between farm types and management practices. Specifically, farms where vaccines were administered by veterinarians showed no significant difference in antibody positivity between Korean native cattle and dairy cattle, regardless of the presence of restraint facilities. However, on farms where vaccinations were conducted by the owners, dairy cattle demonstrated a higher seropositivity (43.30 ± 33.39%) compared to Korean native cattle (21.97 ± 20.79%) in the absence of restraint facilities. Further comparisons underscored the impact of restraint facilities on vaccination efficacy, with dairy farms generally achieving higher antibody positivity (29.43 ± 30.61%) than farms with Korean native cattle (23.02 ± 23.33%) (p &lt; 0.05), suggesting that consistent vaccine delivery methods enhance immunogenic responses. Contrarily, no significant difference was noted in antibody positivity between large- and small-scale farms, indicating that farm size did not notably impact the effectiveness of the vaccinator. These findings emphasize that while current vaccines are sufficiently inducing immunity, enhancing vaccination strategies, particularly through trained personnel and improved restraint facilities, is crucial. This study’s insights into the impact of vaccination and farm management practices provide valuable guidance for refining LSD control measures in Korea and potentially other affected regions.

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE.

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD-CD27- 'double-negative (DN)' DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.

A systematic literature review on public health and healthcare resources for pandemic preparedness planning.

Generating insights into resource demands during outbreaks is an important aspect of pandemic preparedness. The EU PANDEM-2 project used resource modelling to explore the demand profile for key resources during pandemic scenarios. This review aimed to identify public health and healthcare resources needed to respond to pandemic threats and the ranges of parameter values on the use of these resources for pandemic influenza (including the novel influenza A(H1N1)pdm09 pandemic) and the COVID-19 pandemic, to support modelling activities. We conducted a systematic literature review and searched Embase and Medline databases (1995 - June 2023) for articles that included a model, scenario, or simulation of pandemic resources and/or describe resource parameters, for example personal protective equipment (PPE) usage, length of stay (LoS) in intensive care unit (ICU), or vaccine efficacy. Papers with data on resource parameters from all countries were included. We identified 2754 articles of which 147 were included in the final review. Forty-six different resource parameters with values related to non-ICU beds (n = 43 articles), ICU beds (n = 57), mechanical ventilation (n = 39), healthcare workers (n = 12), pharmaceuticals (n = 21), PPE (n = 8), vaccines (n = 26), and testing and tracing (n = 19). Differences between resource types related to pandemic influenza and COVID-19 were observed, for example on mechanical ventilation (mostly for COVID-19) and testing & tracing (all for COVID-19). This review provides an overview of public health and healthcare resources with associated parameters in the context of pandemic influenza and the COVID-19 pandemic. Providing insight into the ranges of plausible parameter values on the use of public health and healthcare resources improves the accuracy of results of modelling different scenarios, and thus decision-making by policy makers and hospital planners. This review also highlights a scarcity of published data on important public health resources.

Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models.

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions.

BIOS-05. PEPTIDE-BASED VACCINES VERSUS DENDRITIC CELL-BASED VACCINE THERAPIES FOR PATIENTS WITH GLIOBLASTOMA: A NETWORK META-ANALYSIS OF CONTROLLED CLINICAL TRIALS

Abstract BACKGROUND Glioblastoma (GBM) is the most prevalent primary CNS malignancy in adults, often with a bleak prognosis. Reports suggest the efficacy of dendritic cell vaccines (DCV) and peptide vaccines in extending overall survival (OS). We aimed to compare their efficacy using network meta-analysis (NMA). METHODS We systematically searched PubMed, Cochrane database, SCOPUS, and Clinicaltrials.gov up to February 2024 for controlled trials on DCV or peptide vaccines for GBM. NMA was conducted using the frequentist approach to obtain direct and indirect comparisons of each vaccine. Pairwise analyses were performed using the inverse variance method, comparing each vaccine’s efficacy. PEPvIII-KLH and Rindopepimut were merged into “Peptide-based vaccines” [PEP], and standard of care (SOC) and (Placebo + SOC) were merged. Primary outcome: hazard ratio (HR) of overall survival with 95% confidence intervals. RESULTS Analysis included 5 studies with 451 patients (vaccine arm) and 445 controls, with SOC/[Placebo + SOC] as reference. Common effects model showed DCV + SOC significantly reduced the HR to 0.3385 [0.1753; 0.6539], while the peptide-based vaccine + SOC reduced the HR to 0.8276 [0.6960; 0.9840]. In the random effects model, DCV + SOC had an HR of 0.3132 [0.0839; 1.1688], and the peptide-based vaccine + SOC had an HR of 0.3888 [0.1383; 1.0928]. Heterogeneity: tau^2 = 0.6473, tau = 0.8045, I^2 = 77.7% [39.5%; 91.8%]. In a pairwise meta-analysis comparing the DCV+SOC and SOC/[Placebo + SOC] consisting of 2 trials, the common and random effects models both estimated an HR of 0.3385 [0.1753; 0.6539, I^2 = 0.0%]. Comparing the PEP+SOC and SOC/[Placebo + SOC] based on 3 trials, the common effect model estimated an HR of 0.8276 [0.6960; 0.9840], while the random effects model estimated an HR of 0.3874 [0.1360; 1.1039, I^2 = 84.4%]. CONCLUSION Based on current evidence, DCV vaccines perform better than peptide-based vaccines in reducing mortality in GBM patients. Further trials are required to validate their efficacies.

Efficacy of Feed-Based Genome-Free Bacterial Vaccine Against Aeromonas hydrophila Infection in Red Tilapia (Oreochromis sp.)

Aeromonas hydrophila causes motile Aeromonas septicemia (MAS), a disease with a high mortality rate in tilapia culture. Feed-based vaccines with the incorporation of inactivated whole-cell bacteria into the feed offer promising tools to control MAS. Currently, the incorporation of genome-free bacteria as bacterial vaccine through the implementation of SimCells® technology into the feed has become a particular interest. Background/Objectives: This study investigates the efficacy of a feed-based vaccine incorporating genome-free A. hydrophila (FBV-GFAH) against MAS infection in red tilapia. Methods: The vaccine was prepared and delivered at 5% fish body weight for three consecutive days in weeks 0 (prime vaccination) and 2 (first booster vaccination), orally. Throughout a five-week experimental period, the immune-related genes (IL-1β, MHC-II, CD4, IgT, and IgM) expression in the hindgut and head kidney of the fish was determined using RT-qPCR assay. Lysozyme (serum) and overall IgM (serum, gut lavage, and skin mucus) productions were also detected. Results: Fish vaccinated with FBV-GFAH showed a significant (p ≤ 0.05) improvement in relative percent survival compared with unvaccinated fish following bacterial challenge. FBV-GFAH induced the expression of immune-related genes in the hindgut and head kidney, especially after booster vaccination. Furthermore, serum lysozyme activity and overall IgM production in serum, skin mucus, and gut lavage were also significantly (p ≤ 0.05) improved in the FBV-GFAH vaccinated fish than the unvaccinated fish. Conclusions: This study showed that FBV-GFAH is a promising feed-based vaccine technology to control MAS in cultured tilapia.

Prophylactic and therapeutic vaccine development: advancements and challenges.

Biomedical research is fundamental in developing preventive and therapeutic vaccines, serving as a cornerstone of global public health. This review explores the key concepts, methodologies, tools, and challenges in the vaccine development landscape, focusing on transitioning from basic biomedical sciences to clinical applications. Foundational disciplines such as virology, immunology, and molecular biology lay the groundwork for vaccine creation, while recent innovations like messenger RNA (mRNA) technology and reverse vaccinology have transformed the field. Additionally, it highlights the role of pharmaceutical advancements in translating lab discoveries into clinical solutions. Techniques like CRISPR-Cas9, genome sequencing, monoclonal antibodies, and computational modeling have significantly enhanced vaccine precision and efficacy, expediting the development of vaccines against infectious diseases. The review also discusses challenges that continue to hinder progress, including stringent regulatory pathways, vaccine hesitancy, and the rapid emergence of new pathogens. These obstacles underscore the need for interdisciplinary collaboration and the adoption of innovative strategies. Integrating personalized medicine, nanotechnology, and artificial intelligence is expected to revolutionize vaccine science further. By embracing these advancements, biomedical research has the potential to overcome existing challenges and usher in a new era of therapeutic and prophylactic vaccines, ultimately improving global health outcomes. This review emphasizes the critical role of vaccines in combating current and future health threats, advocating for continued investment in biomedical science and technology.