Vaccine models predict rules for updating vaccines against evolving pathogens such as SARS-CoV-2 and influenza in the context of pre-existing immunity
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Currently, vaccines for SARS-CoV-2 and influenza viruses are updated if the new vaccine induces higher antibody-titers to circulating variants than current vaccines. This approach does not account for complex dynamics of how prior immunity skews recall responses to the updated vaccine. We: (i) use computational models to mechanistically dissect how prior immunity influences recall responses; (ii) explore how this affects the rules for evaluating and deploying updated vaccines; and (iii) apply this to SARS-CoV-2. Our analysis of existing data suggests that there is a strong benefit to updating the current SARS-CoV-2 vaccines to match the currently circulating variants. We propose a general two-dose strategy for determining if vaccines need updating as well as for vaccinating high-risk individuals. Finally, we directly validate our model by reanalysis of earlier human H5N1 influenza vaccine studies.To determing the efficacy of a single influenza vaccine administration in the elderly receiving annual influenza vaccination, antibody response to influenza vaccine was compared between once and twice injections in a geriatric cohort. Influenza vaccination had been done for 69 inpatients in the year prior to the study, and was administered twice for 34 of them and once for the other 35 during the study period. Influenza vaccine was injected twice to 77 inpatients who had not received influenza vaccine in the year prior to the study.Hemoagglutination inhibition (HI) antibody titer for influenza A/H1N1, A/H3N2, and B was measured before vaccination, after the first vaccination, after the second vaccination, and after the epidemic period, September 1995 to April 1996. HI antibody titer prior to vaccination was significantly higher in the patients who had received influenza vaccination the previous year. The influenza vaccine induced an increase in HI titer in almost all subjects, and the geometric mean of the HI titer after vaccination in the patients who received vaccine once was comparable to that of the patients injected vaccine twice. The number of patients with HI titers of over 128×increased, and the frequency ranged from 60.0% to 97.1% for the influenza viruses of the three subtypes. The frequency of HI titers over 128×was not significantly different among the three groups. The second vaccination did not increase the number of patients with HI titers over 128×when compared with the number after the first injection in the patients who had received influenza vaccine the previous year. These results suggest that prior vaccination does not diminish the antibody response to influenza vaccine in the elderly. The efficacy of a single influenza vaccination is comparable to that achieved by twice injections in the elderly receiving annual influenza vaccination.
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Since 2003, the global panzootic of highly pathogenic avian influenza A (H5N1) among domestic poultry and wild birds has resulted in rare, sporadic, human H5N1 cases of severe respiratory disease with high mortality in Asia, Europe, the Middle East, and Africa. Family clusters of H5N1 cases have been documented, and though most transmission of H5N1 viruses to humans is believed to be directly from sick or dead birds, limited human-to-human transmission of H5N1 viruses has been reported. As H5N1 viruses continue to evolve, the concern for a global influenza pandemic rises.
Highly pathogenic
Pandemic
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Avian influenza viruses may cause mild or severe disease in birds.There have been five recorded outbreaks of highly pathogenic avian influenza in birds in Australia, all of which were caused by the H7 subtype.These were quickly controlled and similar coordinated responses are expected for possible future outbreaks of avian influenza.Migratory birds are not regarded as the source of these outbreaks, and the prevalence of avian influenza viruses in wild birds in Australia is very low.Avian influenza H5N1, which emerged in birds in China in 1996, has spread to bird flocks in Asia, Europe and Africa.The main carriers of avian influenza, ducks, do not migrate to Australia, and currently the risk of H5N1 occurring in Australian birds appears to be low.Nevertheless, surveillance and response plans for outbreaks of highly pathogenic avian influenza have recently been upgraded across Australia.
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The recently reported outbreaks of highly pathogenic avian influenza (HPAI) due to influenza type A/H5N1 in Hungary and then the United Kingdom (UK) have caused considerable disquiet and interest in the agriculture industry and the media.
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Poultry farming
Bird flu
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During the last decade the number of reported outbreaks caused by highly pathogenic avian influenza (HPAI) in domestic poultry has drastically increased. At the same time, low pathogenic avian influenza (LPAI) strains, such as H9N2 in many parts of the Middle East and Asia and H6N2 in live bird markets in California, have become endemic. Each AI outbreak brings the concomitant possibility of poultry-to-human transmission. Indeed, human illness and death have resulted from such occasional transmissions with highly pathogenic avian H7N7 and H5N1 viruses while avian H9N2 viruses have been isolated from individuals with mild influenza. The transmission of avian influenza directly from poultry to humans has brought a sense of urgency in terms of understanding the mechanisms that lead to interspecies transmission of influenza. Domestic poultry species have been previously overlooked as potential intermediate hosts in the generation of influenza viruses with the capacity to infect humans. In this review, we will discuss molecular and epidemiological aspects that have led to the recurrent emergence of avian influenza strains with pandemic potential, with a particular emphasis on the current Asian H5N1 viruses.
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H5N1 genetic structure
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Ongoing outbreaks of H5N1 avian influenza in migratory waterfowl,domestic poultry and humans present a continuing pandemic threat.In this article,the current outbreak of H5N1 in birds and other animals,H5N1 in humans,influenza preparedness plan,vaccine development for H5N1 influenza,medications to treat influenza infection and progress of basic research were reviewed
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In 2021/2022, the re-emergence of highly pathogenic avian influenza (HPAI) occurred in Europe. The outbreak was seeded from two sources: resident and reintroduced viruses, which is unprecedented in the recorded history of avian influenza. The dominant subtype was H5N1, which replaced the H5N8 subtype that had predominated in previous seasons. In this study, we present a whole genome sequence and a phylogenetic analysis of 57 H5N1 HPAI and two low pathogenic avian influenza (LPAI) H5N1 strains collected in the Czech Republic during 2021/2022. Phylogenetic analysis revealed close relationships between H5N1 genomes from poultry and wild birds and secondary transmission in commercial geese. The genotyping showed considerable genetic heterogeneity among Czech H5N1 viruses, with six different HPAI genotypes, three of which were apparently unique. In addition, second-order reassortment relationships were observed with the direct involvement of co-circulating H5N1 LPAI strains. The genetic distance between Czech H5N1 HPAI and the closest LPAI segments available in the database illustrates the profound gaps in our knowledge of circulating LPAI strains. The changing dynamics of HPAI in the wild may increase the likelihood of future HPAI outbreaks and present new challenges in poultry management, biosecurity, and surveillance.
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Biosecurity
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Highly pathogenic avian influenza and in particular the H5N1 strain has resulted in the culling of millions of birds and continues to pose a threat to poultry industries worldwide. The recent outbreak of H5N1 in the UK highlights the need for detailed assessment of the consequences of an incursion and of the efficacy of control strategies. Here, we present results from a model of H5N1 propagation within the British poultry industry. We find that although the majority of randomly seeded incursions do not spread beyond the initial infected premises, there is significant potential for widespread infection. The efficacy of the European Union strategy for disease control is evaluated and our simulations emphasize the pivotal role of duck farms in spreading H5N1.
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Flock
Poultry farming
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