Vaccines for preventing influenza in healthy adults

Demicheli, Vittorio; Rivetti, D; Deeks, John M.; Jefferson, Tom

doi:10.1002/14651858.cd001269.pub2

Cited by 70 publications

(26 citation statements)

References 64 publications

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“…A recent study indicated that the antibody response in seniors was only approximately one-fourth to one-half as rigorous as that in adults <65 years old [14]. Assuming that the vaccine efficacy in terms of preventing deaths is between 70% and 90% of deaths in persons <65 years old [28, 29], this result suggests that the corresponding vaccine efficacy for seniors is between 17% and 53% [14]. Using this range of relative immunogenicity, we estimated the direct effects of vaccination in the different age groups, measured as YLL and deaths prevented per dose of administered vaccine.…”

Section: Methodsmentioning

confidence: 99%

Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost

et al. 2008

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Background How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age. Methods We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure. Results For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those ⩾65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario. Conclusions Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. Flexible setting of vaccination priority is essential to minimize mortality.

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Section: Methodsmentioning

confidence: 99%

Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost

et al. 2008

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“…Infections with unusually virulent strains of the influenza A virus have led to many millions of deaths in a single season, notably during the 1918 influenza pandemic (3). Although vaccination can prevent influenza in 70%–90% of healthy adults (4), vaccines are only protective against a limited range of strains and are not effective against new, potentially pandemic strains. Also, even in the best case scenarios, the rate of protection is less than 40% in high-risk groups such as infants, the elderly, pregnant women, and individuals with weakened immune systems.…”

Section: Introductionmentioning

confidence: 99%

Identification of Influenza Endonuclease Inhibitors Using a Novel Fluorescence Polarization Assay

Baughman

Slavish²,

DuBois³

et al. 2012

ACS Chem. Biol.

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Influenza viruses have been responsible for the largest pandemics in the previous century. Although vaccination and prophylactic antiviral therapeutics are the primary defense against influenza virus, there is a pressing need to develop new antiviral agents to circumvent the limitations of current therapies. The endonuclease activity of the influenza virus PAN protein is essential for virus replication and is a promising target for novel anti-influenza drugs. To facilitate the discovery of endonuclease inhibitors, we have developed a high-throughput fluorescence polarization (FP) assay, utilizing a novel fluorescein-labeled compound (Kd = 0.378 μM) and a PAN construct, to identify small molecules that bind to the PAN endonuclease active site. Several known 4-substituted 2,4-dioxobutanoic acid inhibitors with high and low affinities have been evaluated in this FP-based competitive binding assay, and there was a general correlation between binding and the reported inhibition of endonuclease activity. Additionally, we have demonstrated the utility of this assay for identifying endonuclease inhibitors in a small diverse targeted fragment library. These fragment hits were used to build a follow up library that that led to new active compounds which demonstrate FP binding and anti-influenza activities in plaque inhibition assays. The assay offers significant advantages over previously reported assays, and is suitable for high-throughput and fragment-based screening studies. Additionally the demonstration of the applicability of a mechanism-based ‘targeted fragment’ library supports the general potential of this novel approach for other enzyme targets. These results serve as a sound foundation for the development of new therapeutic leads targeting influenza endonuclease.

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“…In addition, these vaccines induce antibodies primarily to the viral HA and are efficacious in healthy adults, but display lower protective rates in high-risk groups (e.g., the elderly) and may be poorly immunogenic in young children. These problems are compounded once the wild population of virus undergoes significant antigenic drift in the HA component [1], [3], [4], [5], [6]. Consequently, the protective immunity elicited by inactivated vaccines is of too short a duration to protect from newly developed influenza variants.…”

Section: Introductionmentioning

confidence: 99%

Mammalian Expression of Virus-Like Particles for Advanced Mimicry of Authentic Influenza Virus

Yeh

Yang

et al. 2010

PLoS ONE

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BackgroundInfluenza A viruses are major human and animal pathogens with huge economic and societal impact from illness, hospitalizations, and deaths. Virus-like particles (VLPs) of influenza virus have been suggested as a vaccine candidate offering improved safety and efficacy. To develop this concept further, we established a flexible platform to efficiently generate different subtypes of mammalian-expressed influenza VLPs. Here we demonstrate that these mammalian VLPs strongly resemble the authentic viruses in structure, particle size and composition of host factors, and even glycosylation of viral antigens.Methodology/Principal FindingsIn this study, a mammalian VLP system was established by stable co-expression of four influenza structural proteins (HA, NA, M1, and M2) in a Vero cell line. By replacing the surface glycoproteins of HA and NA, we converted the H3N2-VLP subtype to H5N1-VLP. After centrifugation purification of conditioned media, the particle morphologies, average sizes, and hemagglutination abilities of secreted VLPs were characterized, and the VLP constituents were identified by LC/MS/MS. Protease protection assays demonstrated that specific cellular proteins that co-purified with influenza virions were integrated into mammalian VLPs. The glycosylation profiles of mammalian VLPs as revealed by deglycosylation assays were similar to that of progeny viruses produced from Vero cells. Vaccination of mice with 2.5 µg and above of H5N1-VLP elicited H5-specific IgG1 antibodies and resulted in full protection against lethal infection with homologous virus. These results provide compelling evidence that mammalian VLPs closely emulate the exterior of authentic virus particles not only in antigen presentation but also in biological properties and should provide promising vaccine candidates.Conclusions/SignificanceThis flexible mammalian influenza VLP system offers a superior alternative to the conventional reverse genetic vaccine platform without concerns over inadequate presentation of immune antigens or limitations imposed by the manipulation of real viruses.

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Vaccines for preventing influenza in healthy adults

Cited by 70 publications

References 64 publications

Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost

Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost

Identification of Influenza Endonuclease Inhibitors Using a Novel Fluorescence Polarization Assay

Mammalian Expression of Virus-Like Particles for Advanced Mimicry of Authentic Influenza Virus

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