The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform

Montserrat Torremorell - One of the best experts on this subject based on the ideXlab platform.

  • Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity
    Influenza and Other Respiratory Viruses, 2013
    Co-Authors: Andres Diaz, M. Allerson, Marie R. Culhane, Srinand Sreevatsan, Montserrat Torremorell
    Abstract:

    Background The genetic and Antigenic characteristics of influenza A viruses (IAV) within and between species change over time due to Antigenic Shift and drift. Although pigs are known to play a key role in the epidemiology of IAV between species, little is known about the molecular evolution of IAV hemagglutinin (HA) in pigs. Objectives The aim of this study was to evaluate the HA drift of an H1N1 IAV after infecting weaned pigs with or without maternally derived passive immunity. Methods Three- to four-week-old piglets born either to vaccinated or unvaccinated sows were contact-infected upon exposure with an IAV-infected pig. Nasal swabs were collected daily from each pig and tested for IAV by RRT-PCR. Full-length HA sequences were obtained directly from positive nasal swabs and compared between groups. Results Synonymous and non-synonymous mutations were detected in pigs with and without passive immunity. Most of the non-synonymous mutations occurred within the HA1 region of the HA. Changes within HA1 region were only identified in Antigenic site B in pigs without passive immunity and in Antigenic sites A, B, and D in pigs with passive immunity. However, there was no association between the immune status of the pig and the amino acid substitutions observed. Conclusions Overall, we demonstrated that amino acid substitutions within Antigenic sites can happen in weaned pigs with or without passive immunity shortly after infection.

  • Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity.
    Influenza and other respiratory viruses, 2013
    Co-Authors: Andres Diaz, M. Allerson, Marie R. Culhane, Srinand Sreevatsan, Montserrat Torremorell
    Abstract:

    The genetic and Antigenic characteristics of influenza A viruses (IAV) within and between species change over time due to Antigenic Shift and drift. Although pigs are known to play a key role in the epidemiology of IAV between species, little is known about the molecular evolution of IAV hemagglutinin (HA) in pigs. The aim of this study was to evaluate the HA drift of an H1N1 IAV after infecting weaned pigs with or without maternally derived passive immunity. Three- to four-week-old piglets born either to vaccinated or unvaccinated sows were contact-infected upon exposure with an IAV-infected pig. Nasal swabs were collected daily from each pig and tested for IAV by RRT-PCR. Full-length HA sequences were obtained directly from positive nasal swabs and compared between groups. Synonymous and non-synonymous mutations were detected in pigs with and without passive immunity. Most of the non-synonymous mutations occurred within the HA1 region of the HA. Changes within HA1 region were only identified in Antigenic site B in pigs without passive immunity and in Antigenic sites A, B, and D in pigs with passive immunity. However, there was no association between the immune status of the pig and the amino acid substitutions observed. Overall, we demonstrated that amino acid substitutions within Antigenic sites can happen in weaned pigs with or without passive immunity shortly after infection. © 2013 Blackwell Publishing Ltd.

Daniel Stadlbauer - One of the best experts on this subject based on the ideXlab platform.

  • a chimeric hemagglutinin based universal influenza virus vaccine approach induces broad and long lasting immunity in a randomized placebo controlled phase i trial
    Nature Medicine, 2021
    Co-Authors: Raffael Nachbagauer, Jodi Feser, Abdollah Naficy, David I Bernstein, Jeffrey T Guptill, Emmanuel B Walter, Franceso Berlandascorza, Daniel Stadlbauer, Patrick C Wilson, Teresa Aydillo
    Abstract:

    Seasonal influenza viruses constantly change through Antigenic drift and the emergence of pandemic influenza viruses through Antigenic Shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.

  • a chimeric hemagglutinin based universal influenza virus vaccine approach induces broad and long lasting immunity in a randomized placebo controlled phase i trial
    Nature Medicine, 2021
    Co-Authors: Raffael Nachbagauer, Jodi Feser, Abdollah Naficy, David I Bernstein, Jeffrey T Guptill, Emmanuel B Walter, Franceso Berlandascorza, Daniel Stadlbauer
    Abstract:

    Seasonal influenza viruses constantly change through Antigenic drift and the emergence of pandemic influenza viruses through Antigenic Shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18–39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses. New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.

  • Data_Sheet_1_Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model.pdf
    2019
    Co-Authors: Wen-chun Liu, Raffael Nachbagauer, Daniel Stadlbauer, Peter Palese, Alicia Solórzano, Francesco Berlanda-scorza, Adolfo García-sastre, Florian Krammer, Randy A. Albrecht
    Abstract:

    Due to continuous Antigenic drift and occasional Antigenic Shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with “exotic” head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4+IFN-γ+ and CD8+IFN-γ+ effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here.

  • Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model
    Frontiers Media S.A., 2019
    Co-Authors: Raffael Nachbagauer, Daniel Stadlbauer, Wen-chun Liu, Alicia Solórzano, Francesco Berlanda-scorza, Adolfo García-sastre, Peter Palese
    Abstract:

    Due to continuous Antigenic drift and occasional Antigenic Shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with “exotic” head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4+IFN-γ+ and CD8+IFN-γ+ effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here

Honglin Chen - One of the best experts on this subject based on the ideXlab platform.

  • dating the emergence of pandemic influenza viruses
    Proceedings of the National Academy of Sciences of the United States of America, 2009
    Co-Authors: Gavin J D Smith, Justin Bahl, Dhanasekaran Vijaykrishna, Jinxia Zhang, Leo L M Poon, Honglin Chen
    Abstract:

    Pandemic influenza viruses cause significant mortality in humans. In the 20th century, 3 influenza viruses caused major pandemics: the 1918 H1N1 virus, the 1957 H2N2 virus, and the 1968 H3N2 virus. These pandemics were initiated by the introduction and successful adaptation of a novel hemagglutinin subtype to humans from an animal source, resulting in Antigenic Shift. Despite global concern regarding a new pandemic influenza, the emergence pathway of pandemic strains remains unknown. Here we estimated the evolutionary history and inferred date of introduction to humans of each of the genes for all 20th century pandemic influenza strains. Our results indicate that genetic components of the 1918 H1N1 pandemic virus circulated in mammalian hosts, i.e., swine and humans, as early as 1911 and was not likely to be a recently introduced avian virus. Phylogenetic relationships suggest that the A/Brevig Mission/1/1918 virus (BM/1918) was generated by reassortment between mammalian viruses and a previously circulating human strain, either in swine or, possibly, in humans. Furthermore, seasonal and classic swine H1N1 viruses were not derived directly from BM/1918, but their precursors co-circulated during the pandemic. Mean estimates of the time of most recent common ancestor also suggest that the H2N2 and H3N2 pandemic strains may have been generated through reassortment events in unknown mammalian hosts and involved multiple avian viruses preceding pandemic recognition. The possible generation of pandemic strains through a series of reassortment events in mammals over a period of years before pandemic recognition suggests that appropriate surveillance strategies for detection of precursor viruses may abort future pandemics.

Raffael Nachbagauer - One of the best experts on this subject based on the ideXlab platform.

  • a chimeric hemagglutinin based universal influenza virus vaccine approach induces broad and long lasting immunity in a randomized placebo controlled phase i trial
    Nature Medicine, 2021
    Co-Authors: Raffael Nachbagauer, Jodi Feser, Abdollah Naficy, David I Bernstein, Jeffrey T Guptill, Emmanuel B Walter, Franceso Berlandascorza, Daniel Stadlbauer, Patrick C Wilson, Teresa Aydillo
    Abstract:

    Seasonal influenza viruses constantly change through Antigenic drift and the emergence of pandemic influenza viruses through Antigenic Shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.

  • a chimeric hemagglutinin based universal influenza virus vaccine approach induces broad and long lasting immunity in a randomized placebo controlled phase i trial
    Nature Medicine, 2021
    Co-Authors: Raffael Nachbagauer, Jodi Feser, Abdollah Naficy, David I Bernstein, Jeffrey T Guptill, Emmanuel B Walter, Franceso Berlandascorza, Daniel Stadlbauer
    Abstract:

    Seasonal influenza viruses constantly change through Antigenic drift and the emergence of pandemic influenza viruses through Antigenic Shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18–39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses. New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.

  • Data_Sheet_1_Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model.pdf
    2019
    Co-Authors: Wen-chun Liu, Raffael Nachbagauer, Daniel Stadlbauer, Peter Palese, Alicia Solórzano, Francesco Berlanda-scorza, Adolfo García-sastre, Florian Krammer, Randy A. Albrecht
    Abstract:

    Due to continuous Antigenic drift and occasional Antigenic Shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with “exotic” head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4+IFN-γ+ and CD8+IFN-γ+ effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here.

  • Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model
    Frontiers Media S.A., 2019
    Co-Authors: Raffael Nachbagauer, Daniel Stadlbauer, Wen-chun Liu, Alicia Solórzano, Francesco Berlanda-scorza, Adolfo García-sastre, Peter Palese
    Abstract:

    Due to continuous Antigenic drift and occasional Antigenic Shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with “exotic” head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4+IFN-γ+ and CD8+IFN-γ+ effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here

Hao Fang - One of the best experts on this subject based on the ideXlab platform.

  • The medicinal potential of influenza virus surface proteins: hemagglutinin and neuraminidase.
    Current medicinal chemistry, 2011
    Co-Authors: Yuanchao Xie, Jianzhi Gong, Hao Fang
    Abstract:

    Nowadays, influenza virus is still a big threat to human. Hemagglutinin (HA) and neuraminidase (NA) are the two viral surface proteins, which play important roles in the life cycle of influenza virus. Current influenza vaccines and anti-influenza drugs work mainly by interfering with the functions of the two proteins. In this review, we will display some recent studies about the two proteins. As to HA, this review covers a lot including its fusion function, receptor specificity, Antigenic Shift hypothesis, novel antibodies and various inhibitors in order to deeply discuss this protein. As to NA, this review mainly focuses on studies about the newly identified 150-cavity of group-1 NAs and shows some untypical NA inhibitors aiming to provide a broader range of lead compounds for anti-influenza drug design.