scholarly journals Heterosubtypic cross-reactivity of HA1 antibodies to influenza A, with emphasis on nonhuman subtypes (H5N1, H7N7, H9N2)

2017 ◽  
Author(s):  
Dennis E. te Beest ◽  
Erwin de Bruin ◽  
Sandra Imholz ◽  
Marion Koopmans ◽  
Michiel van Boven
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Protein Microarray ◽  
Age Distribution ◽  
Cross Reactivity ◽  
Influenza A Viruses ◽  
Cross Sectional ◽  
Before And After ◽  
2009 H1n1 ◽  
Protein Microarray Analysis

AbstractEpidemics of influenza A vary greatly in size and age distribution of cases, and this variation i attributed to varying levels of pre-existing immunity. Recent studies have shown that antibody mediated immune responses are more cross-reactive than previously believed, and shape patterns of humoral immunity to influenza A viruses over long periods. Here we quantify antibody responses to the hemagglutinin subunit 1 (HA1) across a range of subtypes using protein microarray analysis of cross-sectional serological surveys carried out in the Netherlanc before and after the A/2009 (H1N1) pandemic. We find significant associations of responses, both within and between subtypes. Interestingly, substantial overall reactivity is observed to HA1 of avian H7N7 and H9N2 viruses. Seroprevalence of H7N7 correlates with antibody titer to A/1968 (H3N2), and is highest in persons born between 1954 and 1969. Seroprevalence of H9N2 is high across all ages, and correlates strongly with A/1957 (H2N2). This correlation is most pronounced in A/2009 (H1N1) infected persons born after 1968 who have never encountered A/1957 (H2N2)-like viruses. We conclude that heterosubtypic antibody crossreactivity, both between human subtypes and between human and nonhuman subtypes, is common in the human population.

scholarly journals Three Types of Broadly Reacting Antibodies against Influenza B Viruses Induced by Vaccination with Seasonal Influenza Viruses

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Daisuke Hirano ◽  
Nobuko Ohshima ◽  
Ritsuko Kubota-Koketsu ◽  
Ayami Yamasaki ◽  
Gene Kurosawa ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Mononuclear Cells ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Phage Display Technology ◽  
Display Technology ◽  
2009 H1n1

We analyzed the antibody (Ab) repertoire against influenza B viruses induced by vaccination with seasonal influenza viruses in one individual who had never been vaccinated until 2009. The vaccine used in this study comprised B/Massachusetts/2/2012 (Yamagata lineage), A/Texas/50/2012 (H3N2), and A/California/7/2009 (H1N1). One month after the subject received two vaccinations, blood (200 ml) was obtained and peripheral mononuclear cells were prepared, and a large Ab library was constructed using phage display technology. The library was screened with HA-enriched fraction of B/Massachusetts/2/2012 and B/Brisbane/60/2008 (Victoria lineage) virus, and a total of 26 Abs that potentially bound to hemagglutinin (HA) molecules were isolated. Their binding activities to six influenza B viruses, three of Yamagata lineage and three of Victoria lineage, and two influenza A viruses, H1N1 and H3N2, were examined. The Abs showed cross-reactivity at three different levels. The first type bound to all Yamagata lineage viruses. The second type bound to both Yamagata and Victoria lineage viruses. The third type bound to both influenza A and B viruses. These results indicate that common epitopes exist on HA molecules of influenza virus at various levels, and humans have capability to produce Abs that bind to such common epitopes.

scholarly journals Assessment of exposure to influenza A viruses in pigs between weaning and market age

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Juliana Bonin Ferreira ◽  
Zvonimir Poljak ◽  
Robert Friendship ◽  
Éva Nagy ◽  
Greg Wideman ◽  
...  
Keyword(s):  
Influenza A ◽  
Production Systems ◽  
Influenza A Viruses ◽  
Ha Gene ◽  
Testing Strategies ◽  
Common Causes ◽  
Nasal Swabs ◽  
Antibody Titers ◽  
2009 H1n1 ◽  
Low Prevalence

AbstractInfluenza A viruses (IAVs) are common causes of respiratory infection in pigs. The objective of this study was to characterize the circulation of IAVs between weaning and market age on the basis of development of antibody response and molecular epidemiology of detected viruses. Two batches of weaned pigs were followed in the nursery and finisher barns with a sample of 81 and 75 pigs. Nasal swabs and blood samples were collected from individual pigs for virological and serological analyses. A H3N2 subtype virus, of cluster IV, was detected in Study 1, with a maximum of 97.9% identity to HA gene of viruses previously isolated in Ontario. In Study 2, a H1N1 subtype virus, of 2009 H1N1 pandemic lineage, was detected, with a maximum of 97.8% identity to HA gene of viruses previously isolated in Ontario. On the basis of HA gene, it was observed that pigs were being detected with the same virus over time. The existence of antibody titers for IAV other than the isolated one confirmed that more than one subtype can circulate in the same population. In Study 1, pigs with higher numbers of IAV detection had lower serological titers for the same virus that was confirmed to circulate in the nursery (P < 0.01). Thorough knowledge of all endemic viral strains is fundamental for development of infection and disease control, particularly in complex production systems. This may include consideration of sampling and testing strategies which could detect circulation of all IAV variants, even if they have low prevalence.

scholarly journals Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 708 ◽  
Author(s):  
Aitor Nogales ◽  
Luis Martinez-Sobrido ◽  
David Topham ◽  
Marta DeDiego
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Defense Mechanisms ◽  
Synergistic Effects ◽  
Viral Proteins ◽  
Economic Problem ◽  
Innate Immune ◽  
Host Protein ◽  
Innate Immune Responses ◽  
Influenza A Viruses

Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that the host innate immune system provides restrict IAV replication and infection. Consequently, to successfully replicate in interferon (IFN)-competent systems, IAV has to counteract host antiviral activities, mainly the production of IFN and the activities of IFN-induced host proteins that inhibit virus replication. The IAV multifunctional proteins PA-X and NS1 are virulence factors that modulate the innate immune response and virus pathogenicity. Notably, these two viral proteins have synergistic effects in the inhibition of host protein synthesis in infected cells, although using different mechanisms of action. Moreover, the control of innate immune responses by the IAV NS1 and PA-X proteins is subject to a balance that can determine virus pathogenesis and fitness, and recent evidence shows co-evolution of these proteins in seasonal viruses, indicating that they should be monitored for enhanced virulence. Importantly, inhibition of host gene expression by the influenza NS1 and/or PA-X proteins could be explored to develop improved live-attenuated influenza vaccines (LAIV) by modulating the ability of the virus to counteract antiviral host responses. Likewise, both viral proteins represent a reasonable target for the development of new antivirals for the control of IAV infections. In this review, we summarize the role of IAV NS1 and PA-X in controlling the antiviral response during viral infection.

scholarly journals Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Z. Beau Reneer ◽  
Amanda L. Skarlupka ◽  
Parker J. Jamieson ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Recombinant Proteins ◽  
Human Population ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Global Pandemic

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.

scholarly journals The multifunctional NS1 protein of influenza A viruses

2008 ◽  
Vol 89 (10) ◽  
pp. 2359-2376 ◽  
Author(s):  
Benjamin G. Hale ◽  
Richard E. Randall ◽  
Juan Ortín ◽  
David Jackson
Keyword(s):  
Immune Responses ◽  
Viral Protein ◽  
Influenza A ◽  
Rational Design ◽  
Intracellular Localization ◽  
Cell Physiology ◽  
Ns1 Protein ◽  
Oligoadenylate Synthetase ◽  
Influenza A Viruses ◽  
Viral Protein Synthesis

The non-structural (NS1) protein of influenza A viruses is a non-essential virulence factor that has multiple accessory functions during viral infection. In recent years, the major role ascribed to NS1 has been its inhibition of host immune responses, especially the limitation of both interferon (IFN) production and the antiviral effects of IFN-induced proteins, such as dsRNA-dependent protein kinase R (PKR) and 2'5'-oligoadenylate synthetase (OAS)/RNase L. However, it is clear that NS1 also acts directly to modulate other important aspects of the virus replication cycle, including viral RNA replication, viral protein synthesis, and general host-cell physiology. Here, we review the current literature on this remarkably multifunctional viral protein. In the first part of this article, we summarize the basic biochemistry of NS1, in particular its synthesis, structure, and intracellular localization. We then discuss the various roles NS1 has in regulating viral replication mechanisms, host innate/adaptive immune responses, and cellular signalling pathways. We focus on the NS1–RNA and NS1–protein interactions that are fundamental to these processes, and highlight apparent strain-specific ways in which different NS1 proteins may act. In this regard, the contributions of certain NS1 functions to the pathogenicity of human and animal influenza A viruses are also discussed. Finally, we outline practical applications that future studies on NS1 may lead to, including the rational design and manufacture of influenza vaccines, the development of novel antiviral drugs, and the use of oncolytic influenza A viruses as potential anti-cancer agents.

scholarly journals Pigs with Severe Combined Immunodeficiency Are Impaired in Controlling Influenza A Virus Infection

2016 ◽  
Vol 9 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Daniela S. Rajao ◽  
Crystal L. Loving ◽  
Emily H. Waide ◽  
Phillip C. Gauger ◽  
Jack C.M. Dekkers ◽  
...  
Keyword(s):  
Nk Cells ◽  
Influenza A ◽  
Severe Combined Immunodeficiency ◽  
Lung Pathology ◽  
Combined Immunodeficiency ◽  
Influenza A Viruses ◽  
Nasal Swabs ◽  
2009 H1n1 ◽  
Pulmonary Pathology ◽  
Viral Titers

Influenza A viruses (IAV) infect many host species, including humans and pigs. Severe combined immunodeficiency (SCID) is a condition characterized by a deficiency of T, B, and/or natural killer (NK) cells. Animal models of SCID have great value for biomedical research. Here, we evaluated the pathogenesis and the innate immune response to the 2009 H1N1 pandemic IAV (H1N1pdm09) using a recently identified line of naturally occurring SCID pigs deficient in T and B lymphocytes that still have functional NK cells. SCID pigs challenged with H1N1pdm09 showed milder lung pathology compared to the non-SCID heterozygous carrier pigs. Viral titers in the lungs and nasal swabs of challenged SCID pigs were significantly higher than in carrier pigs 7 days postinfection, despite higher levels of IL-1β and IFN-α in the lungs of SCID pigs. The lower levels of pulmonary pathology were associated with the T and B cell absence in response to infection. The higher viral titers, prolonged shedding, and delayed viral clearance indicated that innate immunity was insufficient for controlling IAV in pigs. This recently identified line of SCID pigs provides a valuable model to understand the immune mechanisms associated with influenza protection and recovery in a natural host.

Sign in / Sign up

Export Citation Format

Share Document