Future epidemiological and economic impacts of universal influenza vaccines.
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ABSTRACT:
SUBMITTER: Sah P
PROVIDER: S-EPMC6789917 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.
| S-EPMC4494237 | biostudies-literature
Project description:Annually recurring seasonal influenza causes massive economic loss and poses severe threats to public health worldwide. The current seasonal influenza vaccines are the most effective means of preventing influenza infections but possess major weaknesses. Seasonal influenza vaccines require annual updating of the vaccine strains. However, it is an unreachable task to accurately predict the future circulating strains. Vaccines with mismatched strains dramatically compromise the vaccine efficacy. In addition, the seasonal influenza vaccines are ineffective against an unpredictable pandemic. A universal influenza vaccine would overcome these weaknesses of the seasonal vaccines and abolish the threat of influenza pandemics. One approach under investigation is to design influenza vaccine immunogens based on conserved, type-specific amino acid sequences and conformational epitopes, rather than strain-specific. Such vaccines can elicit broadly reactive humoral and cellular immunity. Universal influenza vaccine development has intensively employed nanotechnology because the structural and morphological properties of nanoparticles dramatically improve vaccine immunogenicity and the induced immunity duration. Layered protein nanoparticles can decrease off-target immune responses, fine-tune antigen recognition and processing, and facilitate comprehensive immune response induction. Herein, we review the designs of effective nanoparticle universal influenza vaccines, the recent discoveries of specific nanoparticle features that contribute to immunogenicity enhancement, and recent progress in clinical trials.
| S-EPMC8650199 | biostudies-literature
Project description:Influenza affects millions of people worldwide and can result in severe sickness and even death. The best method of prevention is vaccination; however, the seasonal influenza vaccine often suffers from low efficacy and requires yearly vaccination due to changes in strain and viral mutations. More conserved universal influenza antigens like M2 ectodomain (M2e) and the stalk region of hemagglutinin (HA stalk) have been used clinically but often suffer from low antigenicity. To increase antigenicity, universal antigens have been formulated using nano/microparticles as vaccine carriers against influenza. Utilizing polymers, liposomes, metal, and protein-based particles, indicators of immunity and protection in mouse, pig, ferrets, and chicken models of influenza have been shown. In this review, seasonal and universal influenza vaccine formulations comprised of these materials including their physiochemical properties, fabrication, characterization, and biologic responses in vivo are highlighted. The review is concluded with future perspectives for nano/microparticles as carrier systems and other considerations within the universal influenza vaccine delivery landscape. Graphical Abstract.
| S-EPMC8741137 | biostudies-literature
Project description:BackgroundCurrent influenza virus vaccines are effective when well matched to the circulating strains. Unfortunately, antigenic drift and the high diversity of potential emerging zoonotic and pandemic viruses make it difficult to select the right strains for vaccine production. This problem causes vaccine mismatches, which lead to sharp drops in vaccine effectiveness and long response times to manufacture matched vaccines in case of novel pandemic viruses.AimsTo provide an overview of universal influenza virus vaccines and therapeutic antibodies in preclinical and clinical development.SourcesPubMed and clinicaltrials.gov were used as sources for this review.ContentUniversal influenza virus vaccines that target conserved regions of the influenza virus including the haemagglutinin stalk domain, the ectodomain of the M2 ion channel or the internal matrix and nucleoproteins are in late preclinical and clinical development. These vaccines could confer broad protection against all influenza A and B viruses including drift variants and thereby abolish the need for annual re-formulation and re-administration of influenza virus vaccines. In addition, these novel vaccines would enhance preparedness against emerging influenza virus pandemics. Finally, novel therapeutic antibodies against the same conserved targets are in clinical development and could become valuable tools in the fight against influenza virus infection.ImplicationsBoth universal influenza virus vaccines and therapeutic antibodies are potential future options for the control of human influenza infections.
| S-EPMC5389886 | biostudies-literature
Project description:Globally, infection by seasonal influenza viruses causes 3-5 million cases of severe illness and 290,000-650,000 respiratory deaths each year. Various influenza vaccines, including inactivated split- and subunit-type, recombinant and live attenuated vaccines, have been developed since the 1930s when it was discovered that influenza viruses could be cultivated in embryonated eggs. However, the protection rate offered by these vaccines is rather low, especially in very young children and the elderly. In this review, we describe the history of influenza vaccine development, the immune responses induced by the vaccines and the adjuvants applied. Further, we suggest future directions for improving the effectiveness of influenza vaccines in all age groups. This includes the development of an influenza vaccine that induces a balanced T helper cell type 1 and type 2 immune responses based on the understanding of the immune system, and the development of a broad-spectrum influenza vaccine that can increase effectiveness despite antigen shifts and drifts, which are characteristics of the influenza virus. A brighter future can be envisaged if the development of an adjuvant that is safe and effective is realized.
| S-EPMC8209895 | biostudies-literature
Project description:Influenza viruses pose a significant threat to human health. They are responsible for a large number of deaths annually and have a serious impact on the global economy. There are numerous influenza virus subtypes, antigenic variations occur continuously, and epidemic trends are difficult to predict-all of which lead to poor outcomes of routine vaccination against targeted strain subtypes. Therefore, the development of universal influenza vaccines still constitutes the ideal strategy for controlling influenza. This article reviews the progress in development of universal vaccines directed against the conserved regions of hemagglutinin (HA), neuraminidase (NA), and other structural proteins of influenza viruses using new technologies and strategies with the goals of enhancing our understanding of universal influenza vaccines and providing a reference for research into the exploitation of natural immunity against influenza viruses.
| S-EPMC7551969 | biostudies-literature
Project description:Understanding the most important economic impacts of vaccines can provide relevant information to stakeholders when selecting vaccine immunization strategies from a broader perspective. This study was therefore designed to first identify economic impacts to vaccinated individuals and, second, assess the relative importance of these economic impacts. A four-step approach was used, including a review of the literature, a pilot study, and expert consultation. As a fourth step, a survey utilizing a best-worst scaling was conducted among 26 different stakeholders to assess the relative importance of the identified economic impacts. In each of the 15 choice tasks, participants were asked to choose the most important and the least important economic impact from a set of four from the master list. We identified 23 economic impacts relevant for vaccine introduction. Four domains were identified, namely, health related benefits to vaccinated individuals, short- and long-term productivity gains, community or health systems externalities, and broader economic indicators. The first domain was seen as especially important with mortality, health care expenditure, and morbidity ranking in the top three overall. In conclusion, our study suggests that domain A "health related benefits to vaccinated individuals" are valued as more important than the other economic impacts.
| S-EPMC5183751 | biostudies-literature
Project description:The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.
| S-EPMC6631137 | biostudies-literature
Project description:Several candidates of universal influenza vaccine (UIV) have entered phase III clinical trials, which are expected to improve the willingness and coverage of the population substantially. The impact of UIV on the seasonal influenza epidemic in low influenza vaccination coverage regions like China remains unclear. We proposed a new compartmental model involving the transmission of different influenza subtypes to evaluate the effects of UIV. We calibrated the model by weekly surveillance data of influenza in Xi'an City, Shaanxi Province, China, during 2010/11-2018/19 influenza seasons. We calculated the percentage of averted infections under 2-month (September to October) and 6-month (September to the next February) vaccination patterns with varied UIV effectiveness and coverage in each influenza season, compared with no UIV scenario. A total of 195 766 influenza-like illness (ILI) cases were reported during the nine influenza seasons (2010/11-2018/19), of which the highest ILI cases were among age group 0-4 (59.60%) years old, followed by 5-14 (25.22%), 25-59 (8.19%), 15-24 (3.75%) and ⩾60 (3.37%) years old. The influenza-positive rate for all age groups among ILI cases was 17.51%, which is highest among 5-14 (23.75%) age group and followed by 25-59 (16.44%), 15-24 (16.42%), 0-4 (14.66%) and ⩾60 (13.98%) age groups, respectively. Our model showed that UIV might greatly avert influenza infections irrespective of subtypes in each influenza season. For example, in the 2018/19 influenza season, 2-month vaccination pattern with low UIV effectiveness (50%) and coverage (10%), and high UIV effectiveness (75%) and coverage (30%) could avert 41.6% (95% CI 27.8-55.4%) and 83.4% (80.9-85.9%) of influenza infections, respectively; 6-month vaccination pattern with low and high UIV effectiveness and coverage could avert 32.0% (15.9-48.2%) and 74.2% (69.7-78.7%) of influenza infections, respectively. It would need 11.4% (7.9-15.0%) of coverage to reduce half of the influenza infections for 2-month vaccination pattern with low UIV effectiveness and 8.5% (5.0-11.2%) of coverage with high UIV effectiveness, while it would need 15.5% (8.9-20.7%) of coverage for 6-month vaccination pattern with low UIV effectiveness and 11.2% (6.5-15.0%) of coverage with high UIV effectiveness. We conclude that UIV could significantly reduce the influenza infections even for low UIV effectiveness and coverage. The 2-month vaccination pattern could avert more influenza infections than the 6-month vaccination pattern irrespective of influenza subtype and UIV effectiveness and coverage.
| S-EPMC8697312 | biostudies-literature
Project description:Influenza virus is a respiratory pathogen that can cause disease in humans, with symptoms ranging from mild to life-threatening. The vast majority of influenza virus infections in humans are observed during seasonal epidemics and occasional pandemics. Given the substantial public health burden associated with influenza virus infection, yearly vaccination is recommended for protection against seasonal influenza viruses. Despite vigilant surveillance for new variants and careful selection of seasonal vaccine strains, the efficacy of seasonal vaccines can vary widely from year to year. This often results in lowered protection within the population, regardless of vaccination status. In order to broaden the protection afforded by seasonal influenza vaccines, the National Institute of Allergy and Infectious Diseases (NIAID) has deemed the development of a universal influenza virus vaccine to be a priority in influenza virus vaccine research. This universal vaccine would provide protection against all influenza virus strains, eliminating the need for the yearly reformulations of seasonal influenza vaccines. In addition to universal influenza vaccine efforts, substantial progress has been made in developing novel influenza virus therapeutics that utilize broadly neutralizing antibodies to provide protection against influenza virus infection and to mitigate disease outcomes during infection. In this review, we discuss various approaches toward the goal of improving influenza virus vaccine efficacy through a universal influenza virus vaccine. We also address the novel methods of discovery and utilization of broadly neutralizing antibodies to improve influenza disease outcomes.
| S-EPMC7020694 | biostudies-literature