scholarly journals Inactivation of avian influenza viruses by hydrostatic pressure as a potential vaccine development approach

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Shana Priscila Coutinho Barroso ◽  
Ana Clara Vicente dos Santos ◽  
Patrícia Souza dos Santos ◽  
José Nelson dos Santos Silva Couceiro ◽  
Davis Fernandes Ferreira ◽  
...  

Vaccines are a recommended strategy for controlling influenza A infections in humans and animals. Here, we describe the effects of hydrostatic pressure on the structure, morphology and functional characteristics of avian influenza A H3N8 virus. The effect of hydrostatic pressure for 3 h on H3N8 virus revealed that the particles were resistant to this condition, and the virus displayed only a discrete conformational change. We found that pressure of 3 kbar applied for 6 h was able to inhibit haemagglutination and infectivity while virus replication was no longer observed, suggesting that full virus inactivation occurred at this point. However, the neuraminidase activity was not affected at this approach suggesting the maintenance of neutralizing antibody epitopes in this key antigen. Our data bring important information for the area of structural virology of enveloped particles and support the idea of applying pressure-induced inactivation as a tool for vaccine production.

2021 ◽  
Vol 13 (583) ◽  
pp. eabe5449
Author(s):  
Nicole Darricarrère ◽  
Yu Qiu ◽  
Masaru Kanekiyo ◽  
Adrian Creanga ◽  
Rebecca A. Gillespie ◽  
...  

Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus–associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans.


2006 ◽  
Vol 80 (5) ◽  
pp. 2151-2161 ◽  
Author(s):  
Jennifer Humberd ◽  
Yi Guan ◽  
Robert G. Webster

ABSTRACT We investigated the replication and transmission of avian influenza A viruses in two species thought to be intermediate hosts in the spread of influenza A viruses in live poultry markets: Chinese ring-necked pheasants and chukar partridges. All 15 hemagglutinin subtypes replicated in pheasants, and most subtypes transmitted to naïve contact pheasants, primarily via the fecal-oral route. Many viruses were shed from the gastrointestinal tract of experimentally inoculated pheasants for 14 days or longer. Virus was isolated from the cloacal swabs of one contact pheasant for an unprecedented 45 days. Chukar partridges were less susceptible to infection with avian influenza viruses. The viruses that replicated in chukar partridges were isolated for 7 days after experimental inoculation, predominantly from the respiratory tract. We detected high neutralizing antibody titers with correspondingly low levels of serum hemagglutination inhibition antibody titers in pheasants and chukar partridges when chicken red blood cells were used in serological analyses. When horse erythrocytes were used, antibody titers were comparable to those obtained by using the neutralization assay. More importantly, the results suggested that pheasants can serve as a reservoir of influenza virus. Because of their continuous asymptomatic infection and longer stay in the markets, pheasants are ideal “carriers” of influenza A viruses. Their continued presence in live markets contributes to the perpetuation and genetic interaction of influenza viruses there. On the basis of our findings, it does not make good sense to ban quail but not pheasants from the live markets.


2015 ◽  
Vol 90 (4) ◽  
pp. 1872-1879 ◽  
Author(s):  
Xiaoxiao Feng ◽  
Zeng Wang ◽  
Jianzhong Shi ◽  
Guohua Deng ◽  
Huihui Kong ◽  
...  

ABSTRACTWe isolated two H5N1 viruses, A/duck/Hunan/S4020/2008 (DK/08) and A/chicken/Guangxi/S2039/2009 (CK/09), from live-bird markets during routine surveillance and found that these two viruses are genetically similar but differ in their replication and virulence in mice. The CK/09 virus is lethal for mice with a 50% mouse lethal dose (MLD50) of 1.6 log1050% egg infectious doses (EID50), whereas the DK/08 virus is nonpathogenic for mice with an MLD50value of 6.2 log10EID50. We explored the genetic basis of the virulence difference of these two viruses by generating a series of reassortant viruses and mutants in the lethal virus CK/09 background and evaluating their virulence in mice. We found that the PB1 gene of the DK/08 virus dramatically attenuated the virulence of the CK/09 virus and that the amino acid at position 622 in PB1 made an important contribution. We further demonstrated that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impaired the binding of PB1 to viral RNA, thereby dramatically decreasing the polymerase activity and attenuating H5N1 virus virulence in mice. Our results identify a novel virulence-related marker of H5N1 influenza viruses and provide a new target for live attenuated vaccine development.IMPORTANCEH5N1 avian influenza viruses have caused the deaths of nearly 60% of the humans that they have infected since 1997 and clearly represent a threat to public health. A thorough understanding of the genetic basis of virulence determinants will provide important insights for antiviral drug and live attenuated vaccine development. Several virulence-related markers in the PB2, PA, M1, and NS1 proteins of H5N1 viruses have been identified. In this study, we isolated two H5N1 avian influenza viruses that are genetically similar but differ in their virulence in mice, and we identified a new virulence-related marker in the PB1 gene. We found that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impairs the binding of PB1 to viral RNA, thereby attenuating H5N1 virus virulence in mice. This newly identified virulence-related marker could be applied to the development of live attenuated vaccines against H5N1 influenza.


2020 ◽  
Vol 8 (5) ◽  
pp. 778
Author(s):  
Andrew T. Bisset ◽  
Gerard F. Hoyne

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.


2010 ◽  
Vol 11 (1) ◽  
pp. 43-51 ◽  
Author(s):  
E. Paul J. Gibbs ◽  
Tara C. Anderson

AbstractIn the past decade, the pandemics of highly pathogenic avian influenza H5N1 and the novel H1N1 influenza have both illustrated the potential of influenza viruses to rapidly emerge and spread widely in animals and people. Since both of these viruses are zoonotic, these pandemics have been the driving force behind a renewed commitment by the medical and veterinary professions to practice One World, One Health for the control of infectious diseases. The discovery in 2004 that an equine origin H3N8 influenza virus was the cause of an extensive epidemic of respiratory disease in dogs in the USA came as a surprise; at that time dogs were thought to be refractory to infection with influenza viruses. In 2007, a second emerging canine influenza was confirmed in Korea, but this time the causal virus was an H3N2 avian influenza virus. This review focuses on recent events associated with equine and canine influenza viruses. While these viruses do not appear to be zoonotic, the close association between humans and dogs, and to a lesser extent horses, demands that we develop better surveillance and control strategies for emerging diseases in companion animals within the context of One World, One Health.


Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 75 ◽  
Author(s):  
Angita Shrestha ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal

Avian viral diseases including avian influenza, Marek’s disease and Newcastle disease are detrimental to economies around the world that depend on the poultry trade. A significant zoonotic threat is also posed by avian influenza viruses. Vaccination is an important and widely used method for controlling these poultry diseases. However, the current vaccines do not provide full protection or sterile immunity. Hence, there is a need to develop improved vaccines. The major aim of developing improved vaccines is to induce strong and specific humoral and cellular immunity in vaccinated animals. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to antigen-presenting cells (APCs) including dendritic cells, macrophages and B cells. APCs have a central role in the initiation and maintenance of immune responses through their ability to capture, process and present antigens to T and B cells. Vaccine technology that selectively targets APCs has been achieved by coupling antigens to monoclonal antibodies or ligands that are targeted by APCs. The aim of this review is to discuss existing strategies of selective delivery of antigens to APCs for effective vaccine development in poultry.


2019 ◽  
Author(s):  
Wan Yang ◽  
Eric H. Y. Lau ◽  
Benjamin J. Cowling

AbstractInfluenza epidemics cause substantial morbidity and mortality every year worldwide. Currently, two influenza A subtypes, A(H1N1) and A(H3N2), and type B viruses co-circulate in humans and infection with one type/subtype could provide cross-protection against the others. However, it remains unclear how such ecologic competition via cross-immunity and antigenic mutations that allow immune escape impact influenza epidemic dynamics at the population level. Here we develop a comprehensive model-inference system and apply it to study the evolutionary and epidemiological dynamics of the three influenza types/subtypes in Hong Kong, a city of global public health significance for influenza epidemic and pandemic control. Utilizing long-term influenza surveillance data since 1998, we are able to estimate the strength of cross-immunity between each virus-pairs, the timing and frequency of punctuated changes in population immunity in response to antigenic mutations in influenza viruses, and key epidemiological parameters over the last 20 years including the 2009 pandemic. We find evidence of cross-immunity in all types/subtypes, with strongest cross-immunity from A(H1N1) against A(H3N2). Our results also suggest that A(H3N2) may undergo antigenic mutations in both summers and winters and thus monitoring the virus in both seasons may be important for vaccine development. Overall, our study reveals intricate epidemiological interactions and underscores the importance of simultaneous monitoring of population immunity, incidence rates, and viral genetic and antigenic changes.


2021 ◽  
Author(s):  
Bethany J. Hoye ◽  
Celeste M. Donato ◽  
Simeon Lisovski ◽  
Yi-Mo Deng ◽  
Simone Warner ◽  
...  

Australian lineages of avian influenza A viruses (AIVs) are thought to be phylogenetically distinct from those circulating in Eurasia and the Americas, suggesting the circulation of endemic viruses seeded by occasional introductions from other regions. However, processes underlying the introduction, evolution and maintenance of AIVs in Australia remain poorly understood. Waders (Order Charadriiformes, Family Scolopacidae) may play a unique role in the ecology and evolution of AIVs, particularly in Australia, where ducks, geese and swans (Order Anseriformes, Family Anatidae) rarely undertake intercontinental migrations. Across a five-year surveillance period (2011–2015), Ruddy turnstones (Arenaria interpres) that ‘overwinter’ during the Austral summer in south eastern Australia showed generally low levels of AIV prevalence (0–2%). However, in March 2014 we detected AIVs in 32% (95% CI; 25–39%) of individuals in a small, low-density, island population 90km from the Australian mainland. This epizootic comprised three distinct AIV genotypes, each of which represent a unique reassortment of Australian, recently introduced Eurasian, and recently introduced American-lineage gene segments. Strikingly, the Australian-lineage gene segments showed high similarity to H10N7 viruses isolated in 2010 and 2012 from poultry outbreaks 900–1500km to the north. Together with the diverse geographic origins of the American and Eurasian gene segments, these findings suggest extensive circulation and reassortment of AIVs within Australian wild birds over vast geographic distances. Our findings indicate that long-term surveillance in waders may yield unique insights into AIV gene flow, especially in geographic regions like Oceania where Anatidae do not display regular inter- or intracontinental migration. IMPORTANCE High prevalence of avian influenza viruses (AIVs) was detected in a small, low-density, isolated population of Ruddy turnstones in Australia. Analysis of these viruses revealed relatively recent introductions of viral gene segments from both Eurasia and North America, as well as long-term persistence of introduced gene segments in Australian wild birds. These data demonstrate that the flow of viruses into Australia may be more common than initially thought and that, once introduced, these AIVs have the potential to be maintained within the continent. These findings add to a growing body of evidence suggesting Australian wild birds are unlikely to be ecologically-isolated from the highly pathogenic H5Nx viruses circulating among wild birds throughout the northern hemisphere.


2020 ◽  
Vol 94 (11) ◽  
Author(s):  
Yipeng Sun ◽  
Zhe Hu ◽  
Xuxiao Zhang ◽  
Mingyue Chen ◽  
Zhen Wang ◽  
...  

ABSTRACT In the 21st century, the emergence of H7N9 and H1N1/2009 influenza viruses, originating from animals and causing severe human infections, has prompted investigations into the genetic alterations required for cross-species transmission. We previously found that replacement of the human-origin PA gene segment in avian influenza virus (AIV) could overcome barriers to cross-species transmission. Recently, it was reported that the PA gene segment encodes both the PA protein and a second protein, PA-X. Here, we investigated the role of PA-X. We found that an H9N2 avian influenza reassortant virus bearing a human-origin H1N1/2009 PA gene was attenuated in mice after the loss of PA-X. Reverse genetics analyses of PA-X substitutions conserved in human influenza viruses indicated that R195K, K206R, and P210L substitutions conferred significantly increased replication and pathogenicity on H9N2 virus in mice and ferrets. PA-X R195K was present in all human H7N9 and H1N1/2009 viruses and predominated in human H5N6 viruses. Compared with PA-X 195R, H7N9 influenza viruses bearing PA-X 195K showed increased replication and transmission in ferrets. We further showed that PA-X 195K enhanced lung inflammatory responses, potentially due to decreased host shutoff function. A competitive transmission study in ferrets indicated that 195K provides a replicative advantage over 195R in H1N1/2009 viruses. In contrast, PA-X 195K did not influence the virulence of H9N2 AIV in chickens, suggesting that the effects of the substitution were mammal specific. Therefore, future surveillance efforts should scrutinize this region of PA-X because of its potential impact on cross-species transmission of influenza viruses. IMPORTANCE Four influenza pandemics in humans (the Spanish flu of 1918 [H1N1], the Asian flu of 1957 [H2N2], the Hong Kong flu of 1968 [H3N2], and the swine origin flu of 2009 [H1N1]) are all proposed to have been caused by avian or swine influenza viruses that acquired virulence factors through adaptive mutation or reassortment with circulating human viruses. Currently, influenza viruses circulating in animals are repeatedly transmitted to humans, posing a significant threat to public health. However, the molecular properties accounting for interspecies transmission of influenza viruses remain unclear. In the present study, we demonstrated that PA-X plays an important role in cross-species transmission of influenza viruses. At least three human-specific amino acid substitutions in PA-X dramatically enhanced the adaptation of animal influenza viruses in mammals. In particular, PA-X 195K might have contributed to cross-species transmission of H7N9, H5N6, and H1N1/2009 viruses from animal reservoirs to humans.


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