Advances In Vaccine Technology Research Articles

Development and Clinical Applications of Therapeutic Cancer Vaccines with Individualized and Shared Neoantigens.

Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) entail considerable costs and time due to the variable immunogenicity and response rates of these neoantigens-based vaccines, influenced by factors such as neoantigen response, vaccine types, and combination therapy. Given the crucial role of neoantigen efficacy, a number of bioinformatics algorithms and pipelines have been developed to improve the accuracy rate of prediction through considering a series of factors involving in HLA-peptide-TCR complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. On the other hand, shared neoantigens, originating from driver mutations at hot mutation spots (e.g., KRASG12D), offer a promising and ideal target for the development of therapeutic cancer vaccines. A series of clinical practices have established the efficacy of these vaccines in patients with distinct HLA haplotypes. Moreover, increasing evidence demonstrated that a combination of tumor associated antigens (TAAs) and neoantigens can also improve the prognosis, thus expand the repertoire of shared neoantigens for cancer vaccines. In this review, we provide an overview of the complex process involved in identifying personalized neoantigens, their clinical applications, advances in vaccine technology, and explore the therapeutic potential of shared neoantigen strategies.

Vaccines as Immunotherapies for Substance Use Disorders.

Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an optimistic start in animal models over the past 50 years, yielded disappointing results in human clinical trials of vaccines against nicotine, stimulants (cocaine and methamphetamine), and opioids. After a brief review of clinical and selected preclinical vaccine studies, the "lessons learned" from the previous vaccine clinical trials are summarized, and then the newest challenge of a vaccine against fentanyl and its analogs is explored. Animal studies have made significant advances in vaccine technology for SUD treatment over the past 50 years, and the resulting anti-fentanyl vaccines show remarkable promise for ending this epidemic of fentanyl deaths.

Dengue Vaccines: Current Status and Future Perspectives

Dengue fever (DF), caused by the dengue virus (DENV), is a major public health problem worldwide, with approximately 390 million reported annual infections. The lack of specific antiviral therapies and limited means of vector control has led to the development of a dengue vaccine as a promising strategy to combat this disease. The purpose of this review is to provide a comprehensive analysis of the current status and prospects of dengue vaccines. This review describes different approaches used in dengue vaccine development, including live-attenuated, inactivated, subunit, and viral vector vaccines. Each approach is evaluated for immunogenicity, safety, and efficacy based on preclinical and clinical studies, highlighting the strengths and limitations of each vaccine candidate. Future directions and research priorities in dengue vaccine development are highlighted. In conclusion, dengue vaccines have great potential to reduce the burden of DF worldwide. However, some challenges remain regarding vaccine safety, efficacy, delivery, and availability. By addressing these challenges and leveraging advances in vaccine technology, there can be more effective control and prevention of DF and protection of public health, leading to improvement in the quality of life.

Therapeutic Vaccines and Nucleic Acid Drugs for Cardiovascular Disease.

To combat the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), novel vaccine modalities, such as messenger RNA vaccines, were rapidly developed and have shown high efficacy. This new vaccine technology, underpinned by intensive immunological analysis, is now being applied to the production of other vaccines. For over 10 years, we have been developing therapeutic vaccines for non-infectious diseases. The epitope vaccine approach, which combines a B-cell epitope with exogenous T-cell epitopes presented through major histocompatibility complex molecules, has been proposed to induce antibody production. This vaccine type is designed to efficiently induce a blocking antibody response against the self-antigen without activating cytotoxic T cells. If therapeutic vaccines become established as treatment options for conditions such as hypertension or dyslipidemia, their administration-potentially only a few times per year-could replace the need for daily medication. Nucleic acid drugs, including small interfering RNA and antisense oligonucleotides, have recently received attention as long-term agonists, similar to vaccines. Therefore, therapeutic vaccines or nucleic acid drugs could represent a novel strategy for controlling the progression of cardiovascular diseases. It is hoped that the accumulation of immunological findings and advances in vaccine technology will provide valuable insights into the development of vaccines for treating cardiovascular diseases.

Public Sector Contribution to Vaccine Research and Development

This paper explores the public sector’s often undersold role in vaccine research and development (R&D). Further, it examines the recent shift in vaccine innovation policy caused by the urgency of the COVID-19 pandemic. Due to factors such as lack of repetitive dosage, high levels of at-risk investment, and long, large clinical trials, it is difficult to incentivize the private sector to invest in vaccine R&D. To counter these difficulties, vaccine innovation policy focuses on both push and pull incentives to ensure vaccine R&D is proceeding. Government institutions make large at-risk investments to offset the risk for private sector investment into vaccine R&D. Additionally, the government creates innovation policies that make intellectual property rights (IPR) more favourable for those who invest in vaccine R&D. With the removal of IPR for COVID-19 vaccines, the public sector became more instrumental in incentivizing private sector investment, using techniques such as mass ex-ante government vaccine procurement agreements, public-private partnerships, and increased government investments. With more significant government investments in downstream development and manufacturing activities, there is concern that the basic scientific research required for advances in vaccine technology will diminish. With the COVID-19 pandemic still unfolding, it is difficult to determine whether vaccine innovation policy will remain as it is now. However, even if vaccine innovation policy shifts post-pandemic, the public sector must continue to play an important role in vaccine R&D.

Recent Advances in Vaccine Technology for Viral Infection Management: A Spotlight on Next-Generation Vaccines and Nucleic Acid-Based Platforms

Recent advances in vaccine technology and their uses in viral infection management were the focus of the study. Potential nucleic acid-based platforms for vaccine development, including DNA and RNA vaccines, were also investigated. During the COVID-19 pandemic, a lot of attention was paid to RNA-based vaccinations like mRNA vaccines because of their rapid development and scalability. These vaccines were shown to be effective at eliciting protective immune responses and provided the adaptability to include multiple antigenic sites. Preclinical and clinical research of this magnitude is required for the development and assessment of these innovative vaccine methods. Immunogenicity, side effects, and efficacy were all taken into account. The study highlighted the need for more investigation and cooperation between researchers, physicians, and business allies to speed up the process of turning these novel vaccine strategies into successful therapies against different types of viral infections. Our study demonstrated the potential of viral vectors, nanoparticles, and nucleic acid-based platforms in developing vaccine technology, and it contributes important insights into the design and evaluation of innovative vaccine tactics against viral diseases. These results add to the existing body of knowledge and may help direct future antiviral research and development. Keywords: Vaccine development, Viruses, DNA Vaccines, RNA Vaccines, COVID-19 Vaccines

Development and qualification of cell-based relative potency assay for a human respiratory syncytial virus (RSV) mRNA vaccine

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections worldwide. A safe and effective RSV vaccine has been an elusive goal but recent advances in vaccine technology have improved the likelihood that a vaccine for the prevention of RSV could be licensed in near future. We have developed an RSV vaccine V171 consisting of four lipids and messenger ribonucleic acid (mRNA) encoding an engineered form of the RSV F protein stabilized in its prefusion conformation. The lipids form lipid nanoparticles (LNP) with mRNA encapsulated during process, which protects the mRNA from degradation and enables the mRNA to be delivered into mammalian cells. Once inside the cells, the mRNA then can be translated into RSV F protein and elicit both humoral and cellular immune responses. Preclinical results and Phase I clinical trial results indicate that this mRNA vaccine targeting RSV F protein is a promising RSV vaccine approach and should be further evaluated in clinical trials. We have developed a cell-based relative potency assay to support the Phase II development of this vaccine. Test articles and a reference standard are tested with serial dilutions in a 96-well plate pre-seeded with Hep G2 cells. Cells were incubated for 16–18 h after transfection and then permeabilized and stained with a human monoclonal antibody specific to RSV F protein, followed by a fluorophore-conjugated secondary antibody. The plate is then analyzed for percentage of transfected cells and relative potency of the test article is calculated by comparing its EC50 to that of a reference standard. This assay takes advantage of the fact that due to the inherent variability in biological test systems an absolute measure of potency is more variable than a measure of activity relative to a standard. Targeting testing relative potency range 25–250 %, our assay showed an R2 close to 1 for linearity, relative bias of 1.05–5.41 %, and intermediate precision of 11.0 %. The assay has been used for testing of process development samples, formulation development samples, as well as drug product intermediate (DPI) and drug product (DP) in support of Phase II development of our RSV mRNA vaccine.

Progress in vaccine development for infectious diseases-a Keystone Symposia report.

The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.

New Frontiers in the Control of Influenza

In normal times, the Canadian Immunization Conference (CIC) takes place every two years, bringing together public health officials, community advocates, and researchers and clinicians with an interest in vaccines and vaccine- preventable diseases. Due to the COVID-19 pandemic, the conference had not taken place in person since 2018 – in part due to restrictions on travel and gatherings, but also because many attendees were heavily involved in managing the most wide-ranging public health crisis of our time, including the largest mass vaccination campaign in human history. CIC 2023 was a long-awaited opportunity to appreciate the efforts and successes of the response to COVID-19, and to look ahead to how advances in vaccine technologies and improvements in public health processes might help us close a significant gap in immunizations against other vaccine-preventable diseases that occurred over those years. This report will focus on presentations and perspectives relevant to routine immunization programs against seasonal influenza in Canada.

Kanta Subbarao—confronting influenza and COVID-19

Kanta Subbarao—confronting influenza and COVID-19

Vaccine Technologies and Platforms for Infectious Diseases: Current Progress, Challenges, and Opportunities.

Vaccination is a key component of public health policy with demonstrated cost-effective benefits in protecting both human and animal populations. Vaccines can be manufactured under multiple forms including, inactivated (killed), toxoid, live attenuated, Virus-like Particles, synthetic peptide, polysaccharide, polysaccharide conjugate (glycoconjugate), viral vectored (vector-based), nucleic acids (DNA and mRNA) and bacterial vector/synthetic antigen presenting cells. Several processes are used in the manufacturing of vaccines and recent developments in medical/biomedical engineering, biology, immunology, and vaccinology have led to the emergence of innovative nucleic acid vaccines, a novel category added to conventional and subunit vaccines. In this review, we have summarized recent advances in vaccine technologies and platforms focusing on their mechanisms of action, advantages, and possible drawbacks.

To Include or Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity.

Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines focused largely on generating T cell immunity, attention is now aimed at vaccines that generate humoral immunity, either alone or in combination with T cell-based vaccines. High-resolution structures of hepatitis C viral glycoproteins and their interaction with monoclonal antibodies isolated from both cleared and chronically infected people, together with advances in vaccine technologies, provide new avenues for vaccine development.

Vaccine innovations for emerging infectious diseases-a symposium report.

Vaccines have been incredibly successful at stemming the morbidity and mortality of infectious diseases worldwide. However, there are still no effective vaccines for many serious and potentially preventable infectious diseases. Advances in vaccine technology, including new delivery methods and adjuvants, as well as progress in systems biology and an increased understanding of the human immune system, hold the potential to address these issues. In addition, maternal immunization has opened an avenue to address infectious diseases in neonates and very young infants. This report summarizes the presentations from a 1-day symposium at the New York Academy of Sciences entitled "Innovative Vaccines against Resistant Infectious Diseases and Emerging Threats," held on May 20, 2019.

Management of chronic complications associated with herpes zoster ophthalmicus.

Herpes zoster ophthalmicus (HZO) has the potential to cause significant visual morbidity and functional disability in patients with recalcitrant disease, keratitis, and postherpetic neuralgia. This article will review the current methods of prevention and treatment of anterior segment-related chronic complications of HZO. HZO-related anterior segment ocular complications can range to include conjunctivitis, keratitis, and uveitis that can all be difficult to manage. Furthermore, many clinicians differ in their approach to disease management given the relative lack of large randomized controlled trials to guide therapy. The goal in managing complications of HZO is to reduce visual morbidity and to improve analgesia, and here, we present current recommendations for the management of anterior segment complications of HZO. Recent advances in vaccine technology and the initiation of the Zoster Eye Disease Study improve the possibility of reducing the burden of disease while also further standardizing management of HZO.

Recognizing the Importance of Vaccine Confidence

In the past thirty years we have seen dramatic advances in vaccine technology and development that have yielded vaccines to protect against the pneumococcus, Hib, rotavirus, HPV, and meningococcal disease amongst others (Parashar et al., 1998, Gessner and Adegbola, 2008, Khatami and Pollard, 2010, Lynch and Zhanel, 2010). We have also seen a paradigm shift in the availability of these vaccines in the developing world through the efforts of the Gavi alliance and WHO (Fund V). In addition, new vaccines are being developed to target diseases whose primary impact is in developing countries such as the malaria (Wilby et al., 2012) and meningococcal A vaccines (Kristiansen et al., 2013). These changes in technology and the distribution of vaccines have saved many lives and have the potential to save millions more if widespread vaccine use is sustained. Unfortunately, vaccines safety scares and loss of public and political confidence in vaccines and vaccination programs have the potential to negate these public health gains. As we have seen with the polio eradication program in Africa and Asia, bogus vaccine safety concerns and loss of public confidence in the polio vaccination program, whatever the scientific reality, can derail successful programs (Jegede, 2007). Similarly, unfounded vaccine safety concerns regarding the hepatitis B vaccine in France have led to low hepatitis B vaccination rates and persistent disease there (Marshall, 1998).

Reasons for the Low Male Involvement in Routine Child Immunization in Hoima District Uganda using the Attitude, Social Influence and Self Efficacy Model

Millions of children continue to miss immunizations each year despite global increases in financing and advances in vaccine technology. Male involvement in routine child immunization activities could improve and sustain coverage but is rarely emphasized in immunization programs or research. This study identified factors associated with male involvement in routine child immunization using the attitude, social influence and self-efficacy model.A household cluster survey was conducted among 460 fathers aged 18 years or more, with children aged 10-23 months. A semi-structured interviewer-administered questionnaire was used to collect data. Prevalence Risk Ratios (PRRs) were used to measure associations with level of involvement using generalized linear models with Poisson family, log link and robust standard errors in STATA 12. Our findings show that half (51%, 236/460) of the respondents were aged 25-34 years; 36% (166/460) had completed eight or more years of formal education. Although90% (415/460) of the respondents were willing to be involved, only 29% (133/460) were highly involved in routine child immunization. Highly involved fathers had a positive attitude towards involvement in routine child immunization (adj. PRR 2.3, 95% CI 1.18 – 4.98) and were ≥45 years adjusted prevalence risk ratio (adj. PRR) 2.0, 95% confidence interval (CI) 1.15 - 3.76. Traders had a lower involvement compared to those engaged in other occupations (adj. PRR 0.55, 95% CI: 0.37 - 0.82). In conclusion, few fathers were involved in routine child immunization. Strategies to improve fathers’ positive attitude such as health education are needed to increase their involvement, specifically targeting younger fathers and traders.

TUBERCULOSIS AND BRUCELLOSIS IN WOOD BISON (BISON BISON ATHABASCAE) IN NORTHERN CANADA: A RENEWED NEED TO DEVELOP OPTIONS FOR FUTURE MANAGEMENT.

Effective, long-term strategies to manage the threat of bovine tuberculosis and brucellosis spillback from northern, diseased bison to the Canadian cattle herd and adjacent disease-free wood bison (Bison bison athabascae) herds have eluded policy makers in recent decades. A controversial plan to depopulate infected herds and repopulate them with disease-free wood bison was rejected in 1990 because of significant public concern. Since then, technical advances in vaccine technology, genetic salvage, selective culling, and diagnostic test development have occurred. Containment strategies to reduce further spread of these diseases are a necessary first step; recent progress has been made in this area, but challenges remain. This progress has produced more options for management of these herds in northern Canada, and it is time to consider wood bison conservation and long-term disease eradication as equally important goals that must satisfy concerns of conservation groups, agriculture sectors, aboriginal groups, and the general public. Management of wildlife disease reservoirs in other areas, including Yellowstone and Riding Mountain national parks, has demonstrated that effective disease management is possible. Although combinations of different strategies, including vaccination, genetic salvage techniques, and selective culling, that use sensitive and specific diagnostic tests may offer alternatives to depopulation/repopulation, they also have logistic constraints and cost implications that will need consideration in a multistakeholder, collaborative-management framework. We feel the time is right for this discussion, so a long-term solution to this problem can be applied.

Meninigitis immunisation: challenges, successes and new developments

Meningitis, defined as the inflammation of the lining surrounding the spine and the brain, can be caused by bacteria, viruses and fungi. Bacterial meningitis is the most serious form of the disease, causing around 170000 deaths worldwide each year. Most cases of bacterial meningitis are caused by three bacteria-Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type B. In the UK, vaccines are available to combat most of these, yet, according to the Meningitis Research Foundation, around 3400 cases of bacterial meningitis and septicaemia occur every year in the UK and the Republic of Ireland. This article reviews the history of vaccination against meningitis, explores the challenges facing nurses who are at the interface of immunisation policy and public expectations, outlines the current schedule and discusses advances in vaccine technology that offer the potential of a new immunisation against N meningitidis B, the leading cause of meningitis in the UK.

HIV-1 Vaccine Trials: Evolving Concepts and Designs.

An effective prophylactic HIV-1 vaccine is needed to eradicate the HIV/AIDS pandemic but designing such a vaccine is a challenge. Despite many advances in vaccine technology and approaches to generate both humoral and cellular immune responses, major phase-II and -III vaccine trials against HIV/AIDS have resulted in only moderate successes. The modest achievement of the phase-III RV144 prime-boost trial in Thailand re-emphasized the importance of generating robust humoral and cellular responses against HIV. While antibody-directed approaches are being pursued by some groups, others are attempting to develop vaccines targeting cell-mediated immunity, since evidence show CTLs to be important for the control of HIV replication. Phase-I and -IIa multi-epitope vaccine trials have already been conducted with vaccine immunogens consisting of known CTL epitopes conserved across HIV subtypes, but have so far fallen short of inducing robust and consistent anti-HIV CTL responses. The concepts leading to the development of T-cell epitope-based vaccines, the outcomes of related clinical vaccine trials and efforts to enhance the immunogenicity of cell-mediated approaches are summarized in this review. Moreover, we describe a novel approach based on the identification of SIV and FIV antigens which contain conserved HIV-specific T-cell epitopes and represent an alternative method for developing an effective HIV vaccine against global HIV isolates.

Self-boosting vaccines and their implications for herd immunity

Advances in vaccine technology over the past two centuries have facilitated far-reaching impact in the control of many infections, and today's emerging vaccines could likewise open new opportunities in the control of several diseases. Here we consider the potential, population-level effects of a particular class of emerging vaccines that use specific viral vectors to establish long-term, intermittent antigen presentation within a vaccinated host: in essence, "self-boosting" vaccines. In particular, we use mathematical models to explore the potential role of such vaccines in situations where current immunization raises only relatively short-lived protection. Vaccination programs in such cases are generally limited in their ability to raise lasting herd immunity. Moreover, in certain cases mass vaccination can have the counterproductive effect of allowing an increase in severe disease, through reducing opportunities for immunity to be boosted through natural exposure to infection. Such dynamics have been proposed, for example, in relation to pertussis and varicella-zoster virus. In this context we show how self-boosting vaccines could open qualitatively new opportunities, for example by broadening the effective duration of herd immunity that can be achieved with currently used immunogens. At intermediate rates of self-boosting, these vaccines also alleviate the potential counterproductive effects of mass vaccination, through compensating for losses in natural boosting. Importantly, however, we also show how sufficiently high boosting rates may introduce a new regime of unintended consequences, wherein the unvaccinated bear an increased disease burden. Finally, we discuss important caveats and data needs arising from this work.