Accelerate Vaccine Development Research Articles

Accelerate vaccine development using seamless phase 2/3 trial designs

ABSTRACT Background Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines. Research Design and Methods This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, the percentage of early stop, and the accuracy of dose selection. Results On average, when the experimental vaccine was assumed to be effective, the seamless design that performed interim analyses based solely on efficacy saved 555.73 subjects, shortened trials by 10.29 months, and increased power by 3.70%. When the experimental vaccine was less effective than control, it saved an average of 887.73 subjects while maintaining the type I error rate below 0.025. Conclusion The seamless design proves to be a compelling strategy for vaccine development, given its versatility in early stopping, re-estimating sample sizes, and shortening trial durations.

Project lightspeed: A case study in research ethics and accelerated vaccine development

The COVID-19 pathogen led to a fast expanding pandemic because it proved lethal in certain populations but could be transmitted by persons who appeared healthy. As a result, researchers came under unprecedented time pressure to develop a vaccine. This case study focuses on the first COVID-19 vaccine, which was approved for use in humans, known as Comirnaty, the BioNTech-Pfizer COVID-19 vaccine or Vaccine BNT162b2. With the benefit of hindsight, we show how close collaboration with regulators and trust-based decisions meant that the race for a COVID-19 vaccine was won without purposefully infecting healthy participants with an infectious agent that can cause severe illness or death and for which no rescue therapy had existed.

Why is it Important for Family Physicians to Identify Reliable Sources of Information in the Digital Age?

Dear Editor, Accessing reliable information in the 21st century can be challenging, particularly with the ease of access to data through technology. For both society and health professionals, the integrity of information is of utmost importance. Evidence-based medicine (EBM) offers a framework for evaluating the reliability of sources through rigorous scientific methods, including experimentation, falsification, and data accumulation (1). Medical knowledge has historically evolved through continuous refinement, with evidence being established via repeated experiments and analyses. Reliable information stems from multiple confirmations rather than isolated findings. EBM uses a hierarchy of evidence to categorize research by its reliability, facilitating informed clinical decision-making. It presents a structured approach to medical diagnosis, treatment, and follow-up strategies based on evidence levels (Grade Practice Recommendations, A-D) (2). The importance of EBM is emphasized in the digital era, promoting a systematic and reliable presentation of information. To combat misinformation, it is important to exercise critical thinking and skepticism toward information sources. Accessing reliable medical information is of crucial importance, especially in times of crisis such as the COVID-19 pandemic (3). Primary sources, including peer-reviewed journals, respected international guidelines, scientific reports, and reputable textbooks play a pivotal role in providing accurate and trustworthy information. For example, The National Institute for Health and Clinical Excellence (NICE) and the Cochrane Library offer evidence-based information that has undergone peer review (5,6). The pandemic has highlighted the significance of open access to scientific publications, which has facilitated global information sharing and accelerated vaccine development, ultimately reducing morbidity and mortality rates. This event has underscored the necessity of reliable information sources and the importance of continued collaboration and cooperation in the scientific community. Misinformation, particularly on social media, can pose significant challenges when it comes to verifying the accuracy of online information. To differentiate between truth and falsehood, it is crucial to employ critical evaluation methods, such as cross-referencing multiple sources and examining evidence consistency. Educational initiatives on media and health literacy from a young age, as well as platforms dedicated to verifying claims, can play a vital role in countering misinformation (6). In the digital age, family physicians face both opportunities and challenges due to the abundance of online information. It is very important to acknowledge that quick access to a wide range of data is invaluable for informed decision-making in patient care. However, the vast amount of information available also poses the risk of encountering unreliable or outdated sources. Therefore, it is crucial to utilize reputable medical literature and evidence-based resources (7). For family physicians, it is important to remain up-to-date with the latest research and guidelines through respected indexes such as Web of Science, PubMed, and Scopus. This practice not only helps in delivering high-quality patient care but also supports lifelong learning and professional development (8). Additionally, recent global health crises have emphasized the need for quick access to accurate and reliable medical information to effectively address public health emergencies (6). Therefore, discerning and accessing reliable information sources are indispensable skills for family physicians in the digital age. Keywords: evidence-based medicine, information sources, family practice, practice guideline, resource guides

PoxiPred: An Artificial-Intelligence-Based Method for the Prediction of Potential Antigens and Epitopes to Accelerate Vaccine Development Efforts against Poxviruses.

Poxviridae is a family of large, complex, enveloped, and double-stranded DNA viruses. The members of this family are ubiquitous and well known to cause contagious diseases in humans and other types of animals as well. Taxonomically, the poxviridae family is classified into two subfamilies, namely Chordopoxvirinae (affecting vertebrates) and Entomopoxvirinae (affecting insects). The members of the Chordopoxvirinae subfamily are further divided into 18 genera based on the genome architecture and evolutionary relationship. Of these 18 genera, four genera, namely Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, and Yatapoxvirus, are known for infecting humans. Some of the popular members of poxviridae are variola virus, vaccine virus, Mpox (formerly known as monkeypox), cowpox, etc. There is still a pressing demand for the development of effective vaccines against poxviruses. Integrated immunoinformatics and artificial-intelligence (AI)-based methods have emerged as important approaches to design multi-epitope vaccines against contagious emerging infectious diseases. Despite significant progress in immunoinformatics and AI-based techniques, limited methods are available to predict the epitopes. In this study, we have proposed a unique method to predict the potential antigens and T-cell epitopes for multiple poxviruses. With PoxiPred, we developed an AI-based tool that was trained and tested with the antigens and epitopes of poxviruses. Our tool was able to locate 3191 antigen proteins from 25 distinct poxviruses. From these antigenic proteins, PoxiPred redundantly located up to five epitopes per protein, resulting in 16,817 potential T-cell epitopes which were mostly (i.e., 92%) predicted as being reactive to CD8+ T-cells. PoxiPred is able to, on a single run, identify antigens and T-cell epitopes for poxviruses with one single input, i.e., the proteome file of any poxvirus.

Advancements in Vaccine Strategies for Chronic Liver Disease Patients: Navigating Post-COVID Challenges and Opportunities.

This review addresses the vital role of vaccinations in managing patients with chronic liver disease (CLD), especially in the context of the post-COVID-19 landscape. The pandemic has highlighted the unique vulnerabilities of CLD patients, including those awaiting liver transplantation and post-transplant individuals, who face heightened risks of infection due to compromised immune responses. Recent advancements in vaccine technology, such as mRNA platforms, novel adjuvants, and advanced delivery systems, have significantly accelerated vaccine development, enhancing both speed and efficacy. Moreover, the emergence of personalized vaccines, tailored to everyone's unique immunological profile, presents new opportunities, particularly for those with chronic conditions. This review synthesizes the current state of evidence regarding vaccine recommendations for CLD patients, focusing on their response to vaccinations and proposing effective strategies to protect this vulnerable group from vaccine-preventable diseases. It also explores the challenges in implementing these strategies and considers the impact of emerging vaccine delivery systems on improving outcomes for CLD patients. The paper aims to provide nuanced guidance on vaccination in the rapidly evolving healthcare landscape, addressing both technological innovations and comprehensive patient care strategies.

Exploring the ethics of tuberculosis human challenge models

We extend recent conversation about the ethics of human challenge trials to tuberculosis (TB). TB challenge studies could accelerate vaccine development, but ethical concerns regarding risks to trial participants and...

The Implementation of Response Surface Methodology in the Optimization of Lipid Nanoparticle Preparation for Vaccine Development

Lipid nanoparticles (LNPs) are the delivery system behind the success story of mRNA vaccines and the development of DNA and peptide vaccines. LNPs should have particle sizes ranging from 60 to 150 nm for such applications. Achieving such particle size criteria can be challenging in the LNP preparation using a micromixer system with different parameters: i.e., the N/P ratio, aqueous flow rate (AFR) and total flow rate (TFR). Such an issue can be addressed by applying response surface methodology (RSM). Therefore, in this study, we implemented RSM to optimize LNP preparation parameters, including the N/P ratio and AFR. TFR remained constant at 1 mL.min–1 since, from a previous study, it is not a critical parameter for achieving the desired LNP size. Here, we used the pDNA of ACE-2 as a dummy nucleotide. Particle sizes of the resulting LNPs were determined using a dynamic light scattering (DLS) method. Our results indicate that AFR is a significant factor in determining LNP size, whereas the N/P ratio does not have a significant impact on LNP size. We achieved an LNP size of 104.00 nm by applying the N/P ratio of 32.0000 and AFR of 0.9621 mL.min–1. Our results showed that RSM could ease the optimization process in the preparation of LNP, which may support the acceleration of vaccine development. HIGHLIGHTS The significance of lipid nanoparticles (LNPs) as critical delivery systems for mRNA vaccines, DNA vaccines, and peptide vaccines is highlighted The study focuses on addressing the challenge of achieving the desired particle size range during LNP preparation Response surface methodology (RSM) was employed to optimize the N/P ratio and aqueous flow rate for efficient LNP production The study identifies the aqueous flow rate (AFR) as a key factor influencing the size of LNPs Overall, the findings of this study contribute to accelerating vaccine development by streamlining the preparation of LNPs GRAPHICAL ABSTRACT

Artificial intelligence in accelerating vaccine development - current and future perspectives

Tackling antimicrobial resistance requires the development of new drugs and vaccines. Artificial intelligence (AI) assisted computational approaches offer an alternative to the traditionally empirical drug and vaccine discovery pipelines. In this mini review, we focus on the increasingly important role that AI now plays in the development of vaccines and provide the reader with the methods used to identify candidate vaccine candidates for selected multi-drug resistant bacteria.

A feasibility study of controlled human infection with intradermal Bacillus Calmette–Guérin (BCG) injection: Pilot BCG controlled human infection model

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden. Efforts to find novel vaccines are hampered due to the need for large-scale, prolonged, and costly clinical trials. Controlled human infection models (CHIMs) for TB may be used to accelerate vaccine development by ensuring only the most promising vaccine candidates are selected for phase 3 trials, but it is not currently possible to give participants Mycobacterium tuberculosis as a challenge agent. This study aims to replicate and refine an established BCG CHIM at the Liverpool School of Tropical Medicine. Participants will receive an intradermal injection with licensed BCG vaccine (Statens Serum Institut strain). In phase A, participants will undergo punch biopsy two weeks after administration, paired with minimally invasive methods of skin sampling (skin swab, microbiopsy, skin scrape). BCG detection by classical culture and molecular methods will be compared between these techniques and gold standard punch biopsy. Techniques meeting our pre-defined sensitivity and specificity criteria will be applied in Phase B to longitudinally assess intradermal BCG growth two, seven and fourteen days after administration. We will also measure compartmental immune responses in skin, blood and respiratory mucosa in Phase B. This feasibility study will transfer and refine an existing and safe model of BCG controlled human infection. Longitudinal BCG quantification has the potential to increase model sensitivity to detect vaccine and therapeutic responses. If successful, we aim to transfer the model to Malawi in future studies, a setting with endemic TB disease, to accelerate development of vaccines and therapeutics relevant for underserved populations who stand to benefit the most. Registration: ISRCTN: ISRCTN94098600 and ClinicalTrials.gov: NCT0582059

The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK.

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases.

Development of an automated, high-throughput SARS-CoV-2 neutralization assay based on a pseudotyped virus using a vesicular stomatitis virus (VSV) vector

ABSTRACT The global outbreak of COVID-19 has caused a severe threat to human health; therefore, simple, high-throughput neutralization assays are desirable for developing vaccines and drugs against COVID-19. In this study, a high-titre SARS-CoV-2 pseudovirus was successfully packaged by truncating the C-terminus of the SARS-CoV-2 spike protein by 21 amino acids and infecting 293 T cells that had been stably transfected with the angiotensin-converting enzyme 2 (ACE2) receptor and furin (named AF cells), to establish a simple, high-throughput, and automated 384-well plate neutralization assay. The method was optimized for cell amount, virus inoculation, incubation time, and detection time. The automated assay showed good sensitivity, accuracy, reproducibility, Z’ factor, and a good correlation with the live virus neutralization assay. The high-throughput approach would make it available for the SARS-CoV-2 neutralization test in large-scale clinical trials and seroepidemiological surveys which would aid the accelerated vaccine development and evaluation.

Simplifying glycan monitoring of complex antigens such as the SARS-CoV-2 spike to accelerate vaccine development

Glycosylation is a key quality attribute that must be closely monitored for protein therapeutics. Established assays such as HILIC-Fld of released glycans and LC-MS of glycopeptides work well for glycoproteins with a few glycosylation sites but are less amenable for those with multiple glycosylation sites, resulting in complex datasets that are time consuming to generate and difficult to analyze. As part of efforts to improve preparedness for future pandemics, researchers are currently assessing where time can be saved in the vaccine development and production process. In this context, we evaluated if neutral and acidic monosaccharides analysis via HPAEC-PAD could be used as a rapid and robust alternative to LC-MS and HILIC-Fld for monitoring glycosylation between protein production batches. Using glycoengineered spike proteins we show that the HPAEC-PAD monosaccharide assays could quickly and reproducibly detect both major and minor glycosylation differences between batches. Moreover, the monosaccharide results aligned well with those obtained by HILIC-Fld and LC-MS.

Multi-omics for COVID-19: driving development of therapeutics and vaccines

ABSTRACT The ongoing COVID-19 pandemic caused by SARS-CoV-2 has raised global concern for public health and economy. The development of therapeutics and vaccines to combat this virus is continuously progressing. Multi-omics approaches, including genomics, transcriptomics, proteomics, metabolomics, epigenomics and metallomics, have helped understand the structural and molecular features of the virus, thereby assisting in the design of potential therapeutics and accelerating vaccine development for COVID-19. Here, we provide an up-to-date overview of the latest applications of multi-omics technologies in strategies addressing COVID-19, in order to provide suggestions towards the development of highly effective knowledge-based therapeutics and vaccines.

Factors associated with receipt of mRNA-1273 vaccine at a United States national retail pharmacy during the COVID-19 pandemic

IntroductionThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted accelerated vaccine development of novel messenger RNA (mRNA)-based vaccines by Moderna and Pfizer, which received FDA Emergency Use Authorization in December 2020. The purpose of this study was to examine trends in primary series administration and multi-dose completion rates with Moderna’s mRNA-1273 vaccine administered at a United States retail pharmacy. MethodsWalgreens pharmacy data were joined to publicly available data sets to examine trends in mRNA-1273 primary series and multi-dose completion across patient race/ethnicity, age, gender, distance to first vaccination, and community characteristics. Eligible patients received their first dose of mRNA-1273 administered by Walgreens between December 18, 2020 and February 28, 2022. Variables significantly associated with on-time second dose (all patients) and third dose (immunocompromised patients) in univariate analyses were included in linear regression models. A subset of patients in selected states were studied to identify differences in early and late vaccine adoption. ResultsPatients (N = 4,870,915) who received ≥ 1 dose of mRNA-1273 were 57.0% White, 52.6% female, and averaged 49.4 years old. Approximately 85% of patients received a second dose during the study period. Factors associated with on-time second dose administration included older age, race/ethnicity, traveling ≤ 10 miles for the first dose, higher community-level health insurance, and residing in areas with low social vulnerability. Only 51.0% of immunocompromised patients received the third dose as recommended. Factors associated with third dose administration included older age, race/ethnicity, and small-town residence. Early adopters accounted for 60.6% of patients. Factors associated with early adoption included older age, race/ethnicity, and metropolitan residence. ConclusionOver 80% of patients received their on-time second dose of mRNA-1273 vaccine per CDC recommendations. Patient demographics and community characteristics were associated with vaccine receipt and series completion. Novel approaches to facilitate series completion during a pandemic should be further studied.

High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike

Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we establish a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrates a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, we apply this method to a region in the S2 domain that includes the first heptad repeat and central helix. Our results reveal that besides K986P and V987P, several mutations simultaneously improve expression and significantly lower the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.

Modeling the potential health impacts of delayed strain selection on influenza hospitalization and mortality with mRNA vaccines

BackgroundInfluenza viruses are constantly evolving through antigenic drift, which makes vaccines potentially ill-matched to circulating strains due to the time between strain selection and distribution. mRNA technology could improve vaccine effectiveness (VE) by reducing this time. Significant private and public investments would be required to accommodate accelerated vaccine development and approval. Hence, it is important to understand the potential impact of mRNA technology on influenza hospitalizations and mortality. MethodsWe developed an age-stratified dynamic model of influenza transmission to evaluate the potential impact of increased VE (increased protection against either infection or only hospitalization) on hospitalizations and mortality in the United States. We assume that mRNA technology allows for delaying the time to strain choice, which might increase efficacy, but it does not reduce the time needed for distribution and administration, which might reduce availability. To assess this tradeoff, we evaluated two scenarios where strain choice was delayed until late summer resulting in a more effective vaccine available to (1) all age groups by October, or (2) adults 65 years and older starting in August. ResultsIf not available until October, the vaccine would need a minimum of 95% effectiveness against infection to see a decrease in hospitalizations and deaths in all age groups. When delayed until November, even a 100% effective vaccine had no significant impact. For the elderly, the minimum required VE (against infection) was 50% to reduce hospitalizations and deaths. Moreover, a vaccine with 80% VE against infection available in August for the 65 + age group was better than a 95% effective vaccine available in October for all ages. ConclusionsAs the majority of influenza-associated hospitalizations and deaths are in adults 65 years and older, a combination policy targeting higher VE and coverage for this age group in the short term would be the most efficacious.

The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases.

First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2

Capsid virus-like particles (cVLP) have proven safe and immunogenic and can be a versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2. In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center in Nijmegen, Netherlands, and sequentially assigned them to seven groups. Eligible participants were healthy, aged 18-55 years, and tested negative for SARS-CoV-2 and anti-SARS-CoV-2 antibodies. Participants were vaccinated intramuscularly on days 0 and 28 with 6 μg, 12 μg, 25 μg, 50 μg, or 70 μg of the cVLP-based COVID-19 vaccine (ABNCoV2). A subgroup received MF59-adjuvanted ABNCoV2. Follow-up was for 24 weeks after second vaccination. The primary objectives were to assess the safety and tolerability of ABNCoV2 and to identify a dose that optimises the tolerability-immunogenicity ratio 14 days after the first vaccination. The primary safety endpoint was the number of related grade 3 adverse events and serious adverse events in the intention-to-treat population. The primary immunogenicity endpoint was the concentration of ABNCoV2-specific antibodies. The trial is registered with ClinicalTrials.gov, NCT04839146. 45 participants (six to nine per group) were enrolled between March 15 and July 15, 2021. Participants had a total of 249 at least possibly related solicited adverse events (185 grade 1, 63 grade 2, and one grade 3) within a week after vaccination. Two serious adverse events occurred; one was classified as a possible adverse reaction. Antibody titres were dose-dependent with levels plateauing at a vaccination dose of 25-70 μg ABNCoV2. After second vaccination, live virus neutralisation activity against major SARS-CoV-2 variants was high but was lower with an omicron (BA.1) variant. Vaccine-specific IFNγ+ CD4+ T cells were induced. Immunisation with ABNCoV2 was well tolerated, safe, and resulted in a functional immune response. The data support the need for additional clinical development of ABNCoV2 as a second-generation SARS-CoV-2 vaccine. The modular cVLP platform will accelerate vaccine development, beyond SARS-CoV-2. EU, Carlsberg Foundation, and the Novo Nordisk Foundation.

Vaccine clinical trials with dynamic borrowing of historical controls: Two retrospective studies.

Traditional vaccine efficacy trials usually use fixed designs with fairly large sample sizes. Recruiting a large number of subjects requires longer time and higher costs. Furthermore, vaccine developers are more than ever facing the need to accelerate vaccine development to fulfill the public's medical needs. A possible approach to accelerate development is to use the method of dynamic borrowing of historical controls in clinical trials. In this paper, we evaluate the feasibility and the performance of this approach in vaccine development by retrospectively analyzing two real vaccine studies: a relatively small immunological trial (typical early phase study) and a large vaccine efficacy trial (typical Phase 3 study) assessing prophylactic human papillomavirus vaccine. Results are promising, particularly for early development immunological studies, where the adaptive design is feasible, and control of type I error is less relevant.

Human infection challenge in the pandemic era and beyond, HIC-Vac annual meeting report, 2022.

HIC-Vac is an international network of researchers dedicated to developing human infection challenge studies to accelerate vaccine development against pathogens of high global impact. The HIC-Vac Annual Meeting (3rd and 4th November 2022) brought together stakeholders including researchers, ethicists, volunteers, policymakers, industry partners, and funders with a strong representation from low- and middle-income countries. The network enables sharing of research findings, especially in endemic regions. Discussions included pandemic preparedness and the role of human challenge to accelerate vaccine development during outbreak, with industry speakers emphasising the great utility of human challenge in vaccine development. Public consent, engagement, and participation in human challenge studies were addressed, along with the role of embedded social science and empirical studies to uncover social, ethical, and regulatory issues around human infection challenge studies. Study volunteers shared their experiences and motivations for participating in studies. This report summarises completed and ongoing human challenge studies across a variety of pathogens and demographics, and addresses other key issues discussed at the meeting.