Improving seasonal and pandemic influenza vaccines.
Ontology highlight
ABSTRACT:
SUBMITTER: Saville M
PROVIDER: S-EPMC4634120 | biostudies-other | 2008 Nov
REPOSITORIES: biostudies-other
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Project description:Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross-reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non-adjuvanted pre-pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre-pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross-reactive immunogenicity. MF59, the first oil-in-water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59-adjuvanted seasonal influenza vaccine (Fluad has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non-adjuvanted vaccines, and to provide cross-reactive immunity against divergent influenza strains. Similar results have been generated with a MF59-adjuvanted H5N1 pre-pandemic vaccine, which showed higher and broader immunogenicity compared with non-adjuvanted pre-pandemic vaccines.
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Project description:Vaccines will be an important element in mitigating the impact of an influenza pandemic. While research towards developing universal influenza vaccines is ongoing, the current strategy for vaccine supply in a pandemic relies on seasonal influenza vaccine production to be switched over to pandemic vaccines. Understanding how much vaccine could be produced, in which regions of the world and in what timeframe is critical to informing influenza pandemic preparedness. Through the Global Action Plan for Influenza Vaccines, 2006-2016, WHO promoted an increase in vaccine production capacity and monitors the landscape through periodically surveying influenza vaccine manufacturers. This study compares global capacity for production of influenza vaccines in 2019 with estimates from previous surveys; provides an overview of countries with established production facilities; presents vaccine production by type and manufacturing process; and discusses limitations to these estimates. Results of the current survey show that estimated annual seasonal influenza vaccine production capacity changed little since 2015 increasing from 1.47 billion to 1.48 billion doses with potential maximum annual influenza pandemic vaccine production capacity increasing from 6.37 billion to 8.31 billion doses. However, this figure should be interpreted with caution as it presents a best-case scenario with several assumptions which may impact supply. Further, pandemic vaccines would not be immediately available and could take four to six months for first supplies with several more months needed to reach maximum capacity. A moderate-case scenario is also presented of 4.15 billion doses of pandemic vaccine in 12 months. It is important to note that two doses of pandemic vaccine are likely to be required to elicit an adequate immune response. Continued efforts are needed to ensure the sustainability of this production and to conduct research for vaccines that are faster to produce and more broadly protective taking into account lessons learned from COVID-19 vaccine development.
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Project description:The unprecedented global spread of highly pathogenic avian H5N1 influenza viruses within the past ten years and their extreme lethality to poultry and humans has underscored their potential to cause an influenza pandemic. Combating the threat of an impending H5N1 influenza pandemic will require a combination of pharmaceutical and nonpharmaceutical intervention strategies. The emergence of the H1N1 pandemic in 2009 emphasised the unpredictable nature of a pandemic influenza. Undoubtedly, vaccines offer the most viable means to combat a pandemic threat. Current egg-based influenza vaccine manufacturing strategies are unlikely to be able to cater to the huge, rapid global demand because of the anticipated scarcity of embryonated eggs in an avian influenza pandemic and other factors associated with the vaccine production process. Therefore, alternative, egg-independent vaccine manufacturing strategies should be evaluated to supplement the traditional egg-derived influenza vaccine manufacturing. Furthermore, evaluation of dose-sparing strategies that offer protection with a reduced antigen dose will be critical for pandemic influenza preparedness. Development of new antiviral therapeutics and other, nonpharmaceutical intervention strategies will further supplement pandemic preparedness. This review highlights the current status of egg-dependent and egg-independent strategies against an avian influenza pandemic.
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Project description:Hemagglutination inhibiting (HI) antibodies correlate with influenza vaccine protection but their association with protection induced by natural infection has received less attention and was studied here.940 people from 270 unvaccinated households participated in active ILI surveillance spanning 3 influenza seasons. At least 494 provided paired blood samples spanning each season. Influenza infection was confirmed by RT-PCR on nose/throat swabs or serum HI assay conversion.Pre-season homologous HI titer was associated with a significantly reduced risk of infection for H3N2 (OR 0.61, 95%CI 0.44-0.84) and B (0.65, 95%CI 0.54-0.80) strains, but not H1N1 strains, whether re-circulated (OR 0.90, 95%CI 0.71-1.15), new seasonal (OR 0.86, 95%CI 0.54-1.36) or pandemic H1N1-2009 (OR 0.77, 95%CI 0.40-1.49). The risk of seasonal and pandemic H1N1 decreased with increasing age (both p < 0.0001), and the risk of pandemic H1N1 decreased with prior seasonal H1N1 (OR 0.23, 95%CI 0.08-0.62) without inducing measurable A/California/04/2009-like titers.While H1N1 immunity was apparent with increasing age and prior infection, the effect of pre-season HI titer was at best small, and weak for H1N1 compared to H3N2 and B. Antibodies targeting non-HI epitopes may have been more important mediators of infection-neutralizing immunity for H1N1 compared to other subtypes in this setting.
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Project description:Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine-induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross-reactivity.Influenza vaccine-induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age-dependent responses were also analyzed.Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009-2010 and 2010-2011. Serum samples from vaccinated volunteers, age 20-64 years, were collected before and after vaccination with AS03-adjuvanted pandemic and non-adjuvanted trivalent seasonal influenza vaccine that was given 1 year later.Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14-75% of vaccinated had reached antibody titers (?1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57-98%. After primary immunization, younger individuals (20-48 years) had significantly higher antibody titers against all tested viruses than older persons (49-64 years) but this difference disappeared after the seasonal booster vaccination.Even a few amino acid changes in influenza A HA may compromise the vaccine-induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.
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Project description:A live attenuated influenza vaccine (LAIV) is currently approved in the United States for the prevention of influenza in individuals 2-49 years of age. This article summarizes the available data describing the safety and efficacy of LAIV for the prevention of influenza in both children and adults. LAIV is administered as an intranasal spray and has been shown to provide high levels of efficacy against influenza illness caused by both matched and mismatched strains in children and adults. In studies comparing LAIV and inactivated influenza vaccine in children, LAIV recipients experienced 35-53% fewer cases of culture-confirmed influenza illness caused by antigenically matched strains. Protection through a second influenza season against antigenically matched strains has also been seen in children. In adults, definitive comparative studies of LAIV and inactivated vaccine have not been conducted and no statistically significant differences in efficacy have been demonstrated. The most common adverse reactions with LAIV include runny nose/nasal congestion in all age groups, fever >100 degrees F in children, and sore throat in adults. Formulations of LAIV against pandemic influenza strains, including H5N1, H9N2, and H7N3, are currently being tested in preclinical and phase I clinical studies.
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Project description:Influenza B strains represent on average 23% of all circulating strains in Europe and when there is a vaccine mismatch on B strains, additional influenza-related hospitalizations and deaths as well as substantial additional costs are observed. The objective was to estimate the public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines (QIV) compared to trivalent influenza vaccines (TIV) in Europe (EU). Based on data from 5 EU countries (France, Germany, Italy, Spain and UK) during 10 influenza seasons from 2002 to 2013, epidemiological and associated economic outcomes were estimated for each season for the actual scenario where the TIV was used, and for a hypothetical scenario where QIV could have been used instead. By using QIV, this study estimated that for the 5 EU countries, an additional 1.03 million (327.9/100,000 inhabitants) influenza cases, 453,000 (143.9/100,000) general practitioners consultations, 672,000 (213.1/100,000) workdays lost, 24,000 (7.7/100,000) hospitalizations and 10,000 (3.1/100,000) deaths could have been avoided compared to the use of TIV over the 10-seasons-period. This study estimates that QIV can be of economic value since from a societal perspective 15 million Euros would have been saved on general practitioners consultations (14 million Euros from third-party payer perspective), 77 million on hospitalizations (74 million Euros from third-party payer perspective) and 150 million Euros on workdays lost, across the 5 EU countries. In conclusion, the present study estimates that, compared to TIV, QIV may result in a substantial decrease in epidemiological burden and in influenza-related costs.
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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.
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