scholarly journals Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Eugenio J. Abente ◽  
Daniela S. Rajao ◽  
Jefferson Santos ◽  
Bryan S. Kaplan ◽  
Tracy L. Nicholson ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
Rapid Evolution ◽  
The United States ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Partial Protection ◽  
Attenuated Virus ◽  
The Impact

ABSTRACTInfluenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266–8280, 2016,https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses.IMPORTANCEDue to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.

scholarly journals Unseasonal Transmission of H3N2 Influenza A Virus During the Swine-Origin H1N1 Pandemic

2010 ◽  
Vol 84 (11) ◽  
pp. 5715-5718 ◽  
Author(s):  
Elodie Ghedin ◽  
David E. Wentworth ◽  
Rebecca A. Halpin ◽  
Xudong Lin ◽  
Jayati Bera ◽  
...  
Keyword(s):  
New York ◽  
Influenza A Virus ◽  
Influenza A ◽  
New York State ◽  
The United States ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
York State ◽  
Low Incidence ◽  
H3n2 Influenza

ABSTRACT The initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter months. To explore the nature of virus evolution during this influenza “off-season,” we conducted a phylogenetic analysis of H1N1 and H3N2 sequences sampled during April to June 2009 in New York State. Our analysis revealed that multiple lineages of both viruses were introduced and cocirculated during this time, as is typical of influenza virus during the winter. Strikingly, however, we also found strong evidence for the presence of a large transmission chain of H3N2 viruses centered on the south-east of New York State and which continued until at least 1 June 2009. These results suggest that the unseasonal transmission of influenza A viruses may be more widespread than is usually supposed.

scholarly journals Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013

2016 ◽  
Vol 90 (23) ◽  
pp. 10963-10971 ◽  
Author(s):  
Martha I. Nelson ◽  
Karla M. Stucker ◽  
Seth A. Schobel ◽  
Nídia S. Trovão ◽  
Suman R. Das ◽  
...  
Keyword(s):  
United States ◽  
Population Dynamics ◽  
Influenza A Virus ◽  
Influenza A ◽  
The United States ◽  
Viral Population ◽  
Influenza A Viruses ◽  
Swine Industry ◽  
Virus Diversity ◽  
Agricultural Fairs

ABSTRACT The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio ( n = 262) and Indiana ( n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans. IMPORTANCE Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance.

scholarly journals Distinct Nasopharyngeal and Oropharyngeal Microbiota of Children with Influenza A Virus Compared with Healthy Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Zhixin Wen ◽  
Gan Xie ◽  
Qian Zhou ◽  
Chuangzhao Qiu ◽  
Jing Li ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Respiratory Health ◽  
Healthy Children ◽  
Upper Respiratory Tract ◽  
Rdna Sequencing ◽  
The Impact ◽  
Respiratory Microbiome ◽  
Insight Into ◽  
Respiratory Microbiota

Background. Influenza A virus (IAV) has had the highest morbidity globally over the past decade. A growing number of studies indicate that the upper respiratory tract (URT) microbiota plays a key role for respiratory health and that a dysfunctional respiratory microbiota is associated with disease; but the impact of microbiota during influenza is understudied. Methods. We recruited 180 children, including 121 IAV patients and 59 age-matched healthy children. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected to conduct 16S rDNA sequencing and compare microbiota structures in different individuals. Results. Both NP and OP microbiota in IAV patients differed from those in healthy individuals. The NP dominated genera in IVA patients, such as Moraxella, Staphylococcus, Corynebacterium, and Dolosigranulum, showed lower abundance than in healthy children. The Streptococcus significantly enriched in patients’ NP and Phyllobacterium could be generally detected in patients’ NP microbiota. The most abundant genera in OP microbiota showed a decline tendency in patients, including Streptococcus, Neisseria, and Haemophilus. The URT’s bacterial concurrence network changed dramatically in patients. NP and OP samples were clustered into subgroups by different dominant genera; and NP and OP microbiota provided the precise indicators to distinguish IAV patients from healthy children. Conclusion. This is the first respiratory microbiome analysis on pediatric IAV infection which reveals distinct NP and OP microbiota in influenza patients. It provides a new insight into IAV research from the microecology aspect and promotes the understanding of IAV pathogenesis.

scholarly journals Influenza A Virus Reassortment Is Limited by Anatomical Compartmentalization following Coinfection via Distinct Routes

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Mathilde Richard ◽  
Sander Herfst ◽  
Hui Tao ◽  
Nathan T. Jacobs ◽  
Anice C. Lowen
Keyword(s):  
Respiratory Tract ◽  
Influenza A Virus ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Upper Respiratory Tract ◽  
Extrinsic Factors ◽  
Genetic Incompatibility ◽  
Viral Spread ◽  
Virus Reassortment ◽  
The Impact

ABSTRACTExchange of gene segments through reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their reassortment. Using a ferret (Mustella putorius furo) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms.IMPORTANCEGenetic exchange between influenza A viruses (IAVs) through reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits reassortment.

scholarly journals Heterologous Packaging Signals on Segment 4, but Not Segment 6 or Segment 8, Limit Influenza A Virus Reassortment

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Maria C. White ◽  
John Steel ◽  
Anice C. Lowen
Keyword(s):  
Public Health ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Packaging Signal ◽  
Significant Preference ◽  
Virus Reassortment ◽  
Segment 8 ◽  
The Impact ◽  
Packaging Signals

ABSTRACT Influenza A virus (IAV) RNA packaging signals serve to direct the incorporation of IAV gene segments into virus particles, and this process is thought to be mediated by segment-segment interactions. These packaging signals are segment and strain specific, and as such, they have the potential to impact reassortment outcomes between different IAV strains. Our study aimed to quantify the impact of packaging signal mismatch on IAV reassortment using the human seasonal influenza A/Panama/2007/99 (H3N2) and pandemic influenza A/Netherlands/602/2009 (H1N1) viruses. Focusing on the three most divergent segments, we constructed pairs of viruses that encoded identical proteins but differed in the packaging signal regions on a single segment. We then evaluated the frequency with which segments carrying homologous versus heterologous packaging signals were incorporated into reassortant progeny viruses. We found that, when segment 4 (HA) of coinfecting parental viruses was modified, there was a significant preference for the segment containing matched packaging signals relative to the background of the virus. This preference was apparent even when the homologous HA constituted a minority of the HA segment population available in the cell for packaging. Conversely, when segment 6 (NA) or segment 8 (NS) carried modified packaging signals, there was no significant preference for homologous packaging signals. These data suggest that movement of NA and NS segments between the human H3N2 and H1N1 lineages is unlikely to be restricted by packaging signal mismatch, while movement of the HA segment would be more constrained. Our results indicate that the importance of packaging signals in IAV reassortment is segment dependent. IMPORTANCE Influenza A viruses (IAVs) can exchange genes through reassortment. This process contributes to both the highly diverse population of IAVs found in nature and the formation of novel epidemic and pandemic IAV strains. Our study sought to determine the extent to which IAV packaging signal divergence impacts reassortment between seasonal IAVs. Our knowledge in this area is lacking, and insight into the factors that influence IAV reassortment will inform and strengthen ongoing public health efforts to anticipate the emergence of new viruses. We found that the packaging signals on the HA segment, but not the NA or NS segments, restricted IAV reassortment. Thus, the packaging signals of the HA segment could be an important factor in determining the likelihood that two IAV strains of public health interest will undergo reassortment.

scholarly journals Evaluating the role of wild songbirds or rodents in spreading avian influenza virus across an agricultural landscape

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4060 ◽  
Author(s):  
Derek D. Houston ◽  
Shahan Azeem ◽  
Coady W. Lundy ◽  
Yuko Sato ◽  
Baoqing Guo ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Agricultural Landscape ◽  
Clinical Signs ◽  
The United States ◽  
Wild Birds ◽  
Influenza A Viruses

Background Avian influenza virus (AIV) infections occur naturally in wild bird populations and can cross the wildlife-domestic animal interface, often with devastating impacts on commercial poultry. Migratory waterfowl and shorebirds are natural AIV reservoirs and can carry the virus along migratory pathways, often without exhibiting clinical signs. However, these species rarely inhabit poultry farms, so transmission into domestic birds likely occurs through other means. In many cases, human activities are thought to spread the virus into domestic populations. Consequently, biosecurity measures have been implemented to limit human-facilitated outbreaks. The 2015 avian influenza outbreak in the United States, which occurred among poultry operations with strict biosecurity controls, suggests that alternative routes of virus infiltration may exist, including bridge hosts: wild animals that transfer virus from areas of high waterfowl and shorebird densities. Methods Here, we examined small, wild birds (songbirds, woodpeckers, etc.) and mammals in Iowa, one of the regions hit hardest by the 2015 avian influenza epizootic, to determine whether these animals carry AIV. To assess whether influenza A virus was present in other species in Iowa during our sampling period, we also present results from surveillance of waterfowl by the Iowa Department of Natural Resources and Unites Stated Department of Agriculture. Results Capturing animals at wetlands and near poultry facilities, we swabbed 449 individuals, internally and externally, for the presence of influenza A virus and no samples tested positive by qPCR. Similarly, serology from 402 animals showed no antibodies against influenza A. Although several species were captured at both wetland and poultry sites, the overall community structure of wild species differed significantly between these types of sites. In contrast, 83 out of 527 sampled waterfowl tested positive for influenza A via qPCR. Discussion These results suggest that even though influenza A viruses were present on the Iowa landscape at the time of our sampling, small, wild birds and rodents were unlikely to be frequent bridge hosts.

Evolution and antigenic advancement of N2 neuraminidase of swine influenza A viruses circulating in the United States following two separate introductions from human seasonal viruses

2021 ◽  
Author(s):  
Bryan S. Kaplan ◽  
Tavis K. Anderson ◽  
Jennifer Chang ◽  
Jefferson Santos ◽  
Daniel Perez ◽  
...  
Keyword(s):  
United States ◽  
Influenza A Virus ◽  
Influenza A ◽  
Vaccine Development ◽  
Swine Influenza ◽  
The United States ◽  
Antigenic Drift ◽  
Effective Control ◽  
Influenza A Viruses ◽  
Antigenic Diversity

Two separate introductions of human seasonal N2 neuraminidase genes were sustained in United States swine since 1998 (N2-98) and 2002 (N2-02). Herein, we characterized the antigenic evolution of the N2 of swine influenza A virus (IAV) across two decades following each introduction. The N2-98 and N2-02 expanded in genetic diversity, with two statistically supported monophyletic clades within each lineage. To assess antigenic drift in swine N2 following the human-to-swine spillover events, we generated a panel of swine N2 antisera against representative N2 and quantified the antigenic distance between wild-type viruses using enzyme-linked lectin assay and antigenic cartography. The antigenic distance between swine and human N2 was smallest between human N2 circulating at the time of each introduction and the archetypal swine N2. However, sustained circulation and evolution in swine of the two N2 lineages resulted in significant antigenic drift, and the N2-98 and N2-02 swine N2 lineages were antigenically distinct. Although intra-lineage antigenic diversity was observed, the magnitude of antigenic drift did not consistently correlate with the observed genetic differences. These data represent the first quantification of the antigenic diversity of neuraminidase of IAV in swine and demonstrated significant antigenic drift from contemporary human seasonal strains as well as antigenic variation among N2 detected in swine. These data suggest that antigenic mismatch may occur between circulating swine IAV and vaccine strains. Consequently, consideration of the diversity of N2 in swine IAV for vaccine selection may likely result in more effective control, and aid public health initiatives for pandemic preparedness. Importance Antibodies inhibiting the neuraminidase (NA) of influenza A virus (IAV) reduce clinical disease, virus shedding, and transmission, particularly in the absence of neutralizing immunity against the hemagglutinin. To understand antibody recognition of the genetically diverse NA in U.S. swine IAV, we characterized the antigenic diversity of N2 from swine and humans. N2 detected in swine IAV were derived from two distinct human-to-swine spillovers that persisted, are antigenically distinct, and underwent antigenic drift. These findings highlight the need for continued surveillance and vaccine development in swine with increased focus on the NA. Additionally, human seasonal N2 isolated after 2005 were poorly inhibited by representative swine N2 antisera, suggesting a lack of cross-reactive NA antibody mediated immunity between contemporary swine and human N2. Bidirectional transmission between humans and swine represents a One Health challenge, and determining the correlates of immunity to emerging IAV strains is critical to mitigate zoonotic and reverse-zoonotic transmission.

scholarly journals Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 40
Author(s):  
Wen-Chun Liu ◽  
Raffael Nachbagauer ◽  
Daniel Stadlbauer ◽  
Shirin Strohmeier ◽  
Alicia Solórzano ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Virus Vaccine ◽  
Antibody Responses ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Humoral And Cellular Immunity ◽  
Stalk Domain ◽  
One Year

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

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