Virus Vaccine

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Peter Palese - One of the best experts on this subject based on the ideXlab platform.

  • Is a Universal Influenza Virus Vaccine Possible
    Annual review of medicine, 2019
    Co-Authors: Raffael Nachbagauer, Peter Palese
    Abstract:

    Influenza Viruses remain a severe burden to human health because of their contribution to overall morbidity and mortality. Current seasonal influenza Virus Vaccines do not provide sufficient protection to alleviate the annual impact of influenza and cannot confer protection against potentially pandemic influenza Viruses. The lack of protection is due to rapid changes of the viral epitopes targeted by the Vaccine and the often suboptimal immunogenicity of current immunization strategies. Major efforts to improve vaccination approaches are under way. The development of a universal influenza Virus Vaccine may be possible by combining the lessons learned from redirecting the immune response toward conserved viral epitopes, as well as the use of adjuvants and novel vaccination platforms.

  • A mosaic hemagglutinin-based influenza Virus Vaccine candidate protects mice from challenge with divergent H3N2 strains
    npj Vaccines, 2019
    Co-Authors: Felix Broecker, Raffael Nachbagauer, Florian Krammer, Weina Sun, Sean T. H. Liu, Nungruthai Suntronwong, Mark J. Bailey, Peter Palese
    Abstract:

    Current seasonal influenza Virus Vaccines only provide limited, short-lived protection, and antigenic drift in the hemagglutinin surface glycoprotein necessitates their annual re-formulation and re-administration. To overcome these limitations, universal Vaccine strategies that aim at eliciting broadly protective antibodies to conserved epitopes of the hemagglutinin show promise for protecting against diverse and drifted influenza Viruses. Here a vaccination strategy that focuses antibody responses to conserved epitopes of the H3 hemagglutinin is described. The approach is based on antigenic silencing of the immunodominant major antigenic sites of an H3 protein from 2014 by replacing them with corresponding sequences of exotic avian hemagglutinins, yielding “mosaic” hemagglutinins. In mice, vaccination with inactivated Viruses expressing mosaic hemagglutinins induced highly cross-reactive antibodies against the H3 stalk domain that elicited Fc-mediated effector functions in vitro. In addition, the mosaic Viruses elicited head-specific antibodies with neutralizing and hemagglutination-inhibiting activity against recent H3N2 Viruses in vitro. Immune sera protected mice from heterologous challenge with Viruses carrying H3 proteins from 1968 and 1982, whereas immune sera generated with a seasonal Vaccine did not protect. Consequently, the mosaic vaccination approach provides a promising avenue toward a universal influenza Virus Vaccine. Flu Vaccines that target the head domain of the viral hemagglutinin (HA) surface glycoprotein are highly immunogenic, yet the variable nature of this domain across viral strains and its continuous antigenic drift limit Vaccine efficacy. As the HA stalk domain is conserved across influenza Viruses, targeting this region is a promising strategy to generate universal flu Vaccines. However, eliciting high antibody levels against the HA stalk domain and conserved regions in the head domain remains challenging. Here Peter Palese and colleagues at Mount Sinai develop “mosaic” HAs (mHAs) aimed at eliciting antibodies targeting both the stalk domain and epitopes in the head domain outside of the major antigenic sites. These mHAs are based on antigenic silencing of the immunodominant antigenic sites of an H3 protein, which are exchanged with exotic HA sequences from avian influenza Viruses. Vaccination of mice with inactivated Viruses expressing mHAs induced both stalk- and head-specific antibodies active in vitro, and transfer of sera from mice immunized with mHAs was better than sera from mice immunized with a seasonal Vaccine at protecting mice from heterologous challenge with Viruses carrying different H3 proteins, demonstrating the potential of mHAs as universal influenza Virus Vaccine candidates.

  • Is It Possible to Develop a “Universal” Influenza Virus Vaccine? Potential Target Antigens and Critical Aspects for a Universal Influenza Vaccine
    Cold Spring Harbor perspectives in biology, 2018
    Co-Authors: Florian Krammer, Adolfo García-sastre, Peter Palese
    Abstract:

    Influenza Viruses cause seasonal epidemics as well as pandemics and are a significant concern for human health. Current influenza Virus Vaccines show efficacy when they are antigenically well matched to circulating strains. Seasonal influenza Viruses undergo antigenic drift at a high rate and, therefore, current Vaccines have to be reformulated and readministered on an annual basis. Mismatches between Vaccine strains and circulating strains frequently occur, significantly decreasing Vaccine efficacy. In addition, current seasonal influenza Virus Vaccines have limited efficacy against newly emerging pandemic Viruses. A universal influenza Virus Vaccine that induces long-term protection against all influenza Virus strains would abolish the need for annual readministration of seasonal influenza Virus Vaccines and would significantly enhance our pandemic preparedness. Here we discuss the characteristics of universal influenza Virus Vaccines, their potential target antigens, and critical aspects to consider on the path to successfully developing such Vaccines.

  • Advances in Universal Influenza Virus Vaccine Design and Antibody Mediated Therapies Based on Conserved Regions of the Hemagglutinin
    Influenza Pathogenesis and Control - Volume II, 2015
    Co-Authors: Florian Krammer, Peter Palese, John Steel
    Abstract:

    The threat of novel influenza Viruses emerging into the human population from animal reservoirs, as well as the short duration of protection conferred by licensed Vaccines against human seasonal strains has spurred research efforts to improve upon current Vaccines and develop novel therapeutics against influenza Viruses. In recent years these efforts have resulted in the identification of novel, highly conserved epitopes for neutralizing antibodies on the influenza Virus hemagglutinin protein, which are present in both the stalk and globular head domains of the molecule. The existence of such epitopes may allow for generation of novel therapeutic antibodies, in addition to serving as attractive targets of novel Vaccine design. The aims of developing improved Vaccines include eliciting broader protection from drifted strains, inducing long-lived immunity against seasonal strains, and allowing for the rational design of Vaccines that can be stockpiled for use as pre-pandemic Vaccines. In addition, an increased focus on influenza Virus Vaccine research has prompted an improved understanding of how the immune system responds to influenza Virus infection.

  • chimeric hemagglutinin influenza Virus Vaccine constructs elicit broadly protective stalk specific antibodies
    Journal of Virology, 2013
    Co-Authors: Florian Krammer, Natalie Pica, Rong Hai, Irina Margine, Peter Palese
    Abstract:

    Current influenza Virus Vaccine strategies stimulate immune responses toward the globular head domain of the hemagglutinin protein in order to inhibit key steps of the Virus life cycle. Because this domain is highly variable across strains, new Vaccine formulations are required in most years. Here we demonstrate a novel Vaccine strategy that generates immunity to the highly conserved stalk domain by using chimeric hemagglutinin constructs that express unique head and stalk combinations. By repeatedly immunizing mice with constructs that expressed the same stalk but an irrelevant head, we specifically stimulated a stalk-directed response that provided broad-based heterologous and heterosubtypic immunity in mice. Notably, our vaccination scheme provides a universal Vaccine approach that protects against challenge with an H5 subtype Virus. Furthermore, through in vivo studies using passively transferred antibodies or depletion of CD8+ T cells, we demonstrated the critical role that humoral mechanisms of immunity play in the protection observed. The present data suggest that a Vaccine strategy based on the stalk domain of the hemagglutinin protein could be used in humans to broadly protect against a variety of influenza Virus subtypes.

Monique P. Curran - One of the best experts on this subject based on the ideXlab platform.

  • Live Attenuated Measles, Mumps, Rubella, and Varicella Zoster Virus Vaccine (Priorix-Tetra™)
    Pediatric Drugs, 2008
    Co-Authors: Sohita Dhillon, Monique P. Curran
    Abstract:

    ▲ The live attenuated tetravalent Vaccine against measles, mumps, rubella, and varicella zoster Viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) Vaccine and the varicella zoster Virus Vaccine. ▲ The immunogenicity after each dose of a two-dose vaccination course of MMRV Vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster Vaccines, or a single dose of separately administered MMR plus varicella zoster Vaccines followed by a dose of MMR Vaccine, in infants aged 9–24 months. ▲ In infants aged 9–24 months administered a two-dose course of MMRV Vaccine, geometric mean titers for antibodies against all Vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster Virus antibodies (10- to 21-fold). ▲ MMRV as the second vaccination was immunogenic in children aged 5–6 years who had previously received either MMRV or MMR as the first vaccination at 12–24 months of age. ▲ The immunogenicity for measles, mumps, rubella, and varicella zoster Viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polioVirus, and Haemophilus influenzae type b conjugate Vaccine in infants aged 12–23 months. Nor was the immunogenicity of the latter Vaccine altered by coadministration. ▲ The tolerability profile of MMRV Vaccine was comparable to that of separately administered MMR plus varicella zoster Vaccines or of MMR Vaccine alone. Injection-site redness and fever (rectal temperature ≥38°C or axillary temperature ≥37.5°C) were the most frequent adverse events in both groups.

  • Live attenuated measles, mumps, rubella, and varicella zoster Virus Vaccine (Priorix-Tetra).
    Paediatric drugs, 2008
    Co-Authors: Sohita Dhillon, Monique P. Curran
    Abstract:

    The live attenuated tetravalent Vaccine against measles, mumps, rubella, and varicella zoster Viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) Vaccine and the varicella zoster Virus Vaccine. The immunogenicity after each dose of a two-dose vaccination course of MMRV Vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster Vaccines, or a single dose of separately administered MMR plus varicella zoster Vaccines followed by a dose of MMR Vaccine, in infants aged 9-24 months. In infants aged 9-24 months administered a two-dose course of MMRV Vaccine, geometric mean titers for antibodies against all Vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster Virus antibodies (10- to 21-fold). MMRV as the second vaccination was immunogenic in children aged 5-6 years who had previously received either MMRV or MMR as the first vaccination at 12-24 months of age. The immunogenicity for measles, mumps, rubella, and varicella zoster Viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polioVirus, and Haemophilus influenzae type b conjugate Vaccine in infants aged 12-23 months. Nor was the immunogenicity of the latter Vaccine altered by coadministration. The tolerability profile of MMRV Vaccine was comparable to that of separately administered MMR plus varicella zoster Vaccines or of MMR Vaccine alone. Injection-site redness and fever (rectal temperature > or =38degreesC or axillary temperature > or =37.5degreesC) were the most frequent adverse events in both groups.

Sohita Dhillon - One of the best experts on this subject based on the ideXlab platform.

  • Live Attenuated Measles, Mumps, Rubella, and Varicella Zoster Virus Vaccine (Priorix-Tetra™)
    Pediatric Drugs, 2008
    Co-Authors: Sohita Dhillon, Monique P. Curran
    Abstract:

    ▲ The live attenuated tetravalent Vaccine against measles, mumps, rubella, and varicella zoster Viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) Vaccine and the varicella zoster Virus Vaccine. ▲ The immunogenicity after each dose of a two-dose vaccination course of MMRV Vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster Vaccines, or a single dose of separately administered MMR plus varicella zoster Vaccines followed by a dose of MMR Vaccine, in infants aged 9–24 months. ▲ In infants aged 9–24 months administered a two-dose course of MMRV Vaccine, geometric mean titers for antibodies against all Vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster Virus antibodies (10- to 21-fold). ▲ MMRV as the second vaccination was immunogenic in children aged 5–6 years who had previously received either MMRV or MMR as the first vaccination at 12–24 months of age. ▲ The immunogenicity for measles, mumps, rubella, and varicella zoster Viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polioVirus, and Haemophilus influenzae type b conjugate Vaccine in infants aged 12–23 months. Nor was the immunogenicity of the latter Vaccine altered by coadministration. ▲ The tolerability profile of MMRV Vaccine was comparable to that of separately administered MMR plus varicella zoster Vaccines or of MMR Vaccine alone. Injection-site redness and fever (rectal temperature ≥38°C or axillary temperature ≥37.5°C) were the most frequent adverse events in both groups.

  • Live attenuated measles, mumps, rubella, and varicella zoster Virus Vaccine (Priorix-Tetra).
    Paediatric drugs, 2008
    Co-Authors: Sohita Dhillon, Monique P. Curran
    Abstract:

    The live attenuated tetravalent Vaccine against measles, mumps, rubella, and varicella zoster Viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) Vaccine and the varicella zoster Virus Vaccine. The immunogenicity after each dose of a two-dose vaccination course of MMRV Vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster Vaccines, or a single dose of separately administered MMR plus varicella zoster Vaccines followed by a dose of MMR Vaccine, in infants aged 9-24 months. In infants aged 9-24 months administered a two-dose course of MMRV Vaccine, geometric mean titers for antibodies against all Vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster Virus antibodies (10- to 21-fold). MMRV as the second vaccination was immunogenic in children aged 5-6 years who had previously received either MMRV or MMR as the first vaccination at 12-24 months of age. The immunogenicity for measles, mumps, rubella, and varicella zoster Viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polioVirus, and Haemophilus influenzae type b conjugate Vaccine in infants aged 12-23 months. Nor was the immunogenicity of the latter Vaccine altered by coadministration. The tolerability profile of MMRV Vaccine was comparable to that of separately administered MMR plus varicella zoster Vaccines or of MMR Vaccine alone. Injection-site redness and fever (rectal temperature > or =38degreesC or axillary temperature > or =37.5degreesC) were the most frequent adverse events in both groups.

Thomas P. Monath - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy of Killed Virus Vaccine, Live Attenuated Chimeric Virus Vaccine, and Passive Immunization for Prevention of West Nile Virus Encephalitis in Hamster Model
    Emerging infectious diseases, 2002
    Co-Authors: Robert B. Tesh, Juan Arroyo, Amelia P. A. Travassos Da Rosa, Hilda Guzman, Shu-yuan Xiao, Thomas P. Monath
    Abstract:

    Results of experiments evaluating the efficacy of three immunization strategies for the prevention of West Nile Virus (WNV) encephalitis are reported. Immunization strategies evaluated included a killed Virus veterinary Vaccine, a live attenuated chimeric Virus Vaccine candidate, and passive immunization with WNV-immune serum; all were tested by using a hamster model of the disease. Each product protected the animals from clinical illness and death when challenged with a hamster-virulent éwild-type WNV strain 1 month after initial immunization. The live attenuated chimeric Virus Vaccine candidate induced the highest humoral antibody responses, as measured by hemagglutination inhibition, complement fixation, and plaque reduction neutralization tests. Although the duration of protective immunity was not determined in this study, our preliminary results and the cumulative experience of other Virus Vaccines suggest that the live attenuated chimeric Virus provides the longest lasting immunity.

  • Yellow fever vector live-Virus Vaccines: West Nile Virus Vaccine development.
    Trends in molecular medicine, 2001
    Co-Authors: Juan Pablo Arroyo, Charles A Miller, John Catalan, Thomas P. Monath
    Abstract:

    By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA Virus Vaccine, has been manipulated to induce a protective immune response against Viruses of the same family (e.g. Japanese encephalitis and dengue Viruses). Triggered by the emergence of West Nile Virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-Virus attenuated candidate Vaccine against West Nile Virus.

Florian Krammer - One of the best experts on this subject based on the ideXlab platform.

  • A mosaic hemagglutinin-based influenza Virus Vaccine candidate protects mice from challenge with divergent H3N2 strains
    npj Vaccines, 2019
    Co-Authors: Felix Broecker, Raffael Nachbagauer, Florian Krammer, Weina Sun, Sean T. H. Liu, Nungruthai Suntronwong, Mark J. Bailey, Peter Palese
    Abstract:

    Current seasonal influenza Virus Vaccines only provide limited, short-lived protection, and antigenic drift in the hemagglutinin surface glycoprotein necessitates their annual re-formulation and re-administration. To overcome these limitations, universal Vaccine strategies that aim at eliciting broadly protective antibodies to conserved epitopes of the hemagglutinin show promise for protecting against diverse and drifted influenza Viruses. Here a vaccination strategy that focuses antibody responses to conserved epitopes of the H3 hemagglutinin is described. The approach is based on antigenic silencing of the immunodominant major antigenic sites of an H3 protein from 2014 by replacing them with corresponding sequences of exotic avian hemagglutinins, yielding “mosaic” hemagglutinins. In mice, vaccination with inactivated Viruses expressing mosaic hemagglutinins induced highly cross-reactive antibodies against the H3 stalk domain that elicited Fc-mediated effector functions in vitro. In addition, the mosaic Viruses elicited head-specific antibodies with neutralizing and hemagglutination-inhibiting activity against recent H3N2 Viruses in vitro. Immune sera protected mice from heterologous challenge with Viruses carrying H3 proteins from 1968 and 1982, whereas immune sera generated with a seasonal Vaccine did not protect. Consequently, the mosaic vaccination approach provides a promising avenue toward a universal influenza Virus Vaccine. Flu Vaccines that target the head domain of the viral hemagglutinin (HA) surface glycoprotein are highly immunogenic, yet the variable nature of this domain across viral strains and its continuous antigenic drift limit Vaccine efficacy. As the HA stalk domain is conserved across influenza Viruses, targeting this region is a promising strategy to generate universal flu Vaccines. However, eliciting high antibody levels against the HA stalk domain and conserved regions in the head domain remains challenging. Here Peter Palese and colleagues at Mount Sinai develop “mosaic” HAs (mHAs) aimed at eliciting antibodies targeting both the stalk domain and epitopes in the head domain outside of the major antigenic sites. These mHAs are based on antigenic silencing of the immunodominant antigenic sites of an H3 protein, which are exchanged with exotic HA sequences from avian influenza Viruses. Vaccination of mice with inactivated Viruses expressing mHAs induced both stalk- and head-specific antibodies active in vitro, and transfer of sera from mice immunized with mHAs was better than sera from mice immunized with a seasonal Vaccine at protecting mice from heterologous challenge with Viruses carrying different H3 proteins, demonstrating the potential of mHAs as universal influenza Virus Vaccine candidates.

  • Is It Possible to Develop a “Universal” Influenza Virus Vaccine? Potential Target Antigens and Critical Aspects for a Universal Influenza Vaccine
    Cold Spring Harbor perspectives in biology, 2018
    Co-Authors: Florian Krammer, Adolfo García-sastre, Peter Palese
    Abstract:

    Influenza Viruses cause seasonal epidemics as well as pandemics and are a significant concern for human health. Current influenza Virus Vaccines show efficacy when they are antigenically well matched to circulating strains. Seasonal influenza Viruses undergo antigenic drift at a high rate and, therefore, current Vaccines have to be reformulated and readministered on an annual basis. Mismatches between Vaccine strains and circulating strains frequently occur, significantly decreasing Vaccine efficacy. In addition, current seasonal influenza Virus Vaccines have limited efficacy against newly emerging pandemic Viruses. A universal influenza Virus Vaccine that induces long-term protection against all influenza Virus strains would abolish the need for annual readministration of seasonal influenza Virus Vaccines and would significantly enhance our pandemic preparedness. Here we discuss the characteristics of universal influenza Virus Vaccines, their potential target antigens, and critical aspects to consider on the path to successfully developing such Vaccines.

  • Advances in Universal Influenza Virus Vaccine Design and Antibody Mediated Therapies Based on Conserved Regions of the Hemagglutinin
    Influenza Pathogenesis and Control - Volume II, 2015
    Co-Authors: Florian Krammer, Peter Palese, John Steel
    Abstract:

    The threat of novel influenza Viruses emerging into the human population from animal reservoirs, as well as the short duration of protection conferred by licensed Vaccines against human seasonal strains has spurred research efforts to improve upon current Vaccines and develop novel therapeutics against influenza Viruses. In recent years these efforts have resulted in the identification of novel, highly conserved epitopes for neutralizing antibodies on the influenza Virus hemagglutinin protein, which are present in both the stalk and globular head domains of the molecule. The existence of such epitopes may allow for generation of novel therapeutic antibodies, in addition to serving as attractive targets of novel Vaccine design. The aims of developing improved Vaccines include eliciting broader protection from drifted strains, inducing long-lived immunity against seasonal strains, and allowing for the rational design of Vaccines that can be stockpiled for use as pre-pandemic Vaccines. In addition, an increased focus on influenza Virus Vaccine research has prompted an improved understanding of how the immune system responds to influenza Virus infection.

  • chimeric hemagglutinin influenza Virus Vaccine constructs elicit broadly protective stalk specific antibodies
    Journal of Virology, 2013
    Co-Authors: Florian Krammer, Natalie Pica, Rong Hai, Irina Margine, Peter Palese
    Abstract:

    Current influenza Virus Vaccine strategies stimulate immune responses toward the globular head domain of the hemagglutinin protein in order to inhibit key steps of the Virus life cycle. Because this domain is highly variable across strains, new Vaccine formulations are required in most years. Here we demonstrate a novel Vaccine strategy that generates immunity to the highly conserved stalk domain by using chimeric hemagglutinin constructs that express unique head and stalk combinations. By repeatedly immunizing mice with constructs that expressed the same stalk but an irrelevant head, we specifically stimulated a stalk-directed response that provided broad-based heterologous and heterosubtypic immunity in mice. Notably, our vaccination scheme provides a universal Vaccine approach that protects against challenge with an H5 subtype Virus. Furthermore, through in vivo studies using passively transferred antibodies or depletion of CD8+ T cells, we demonstrated the critical role that humoral mechanisms of immunity play in the protection observed. The present data suggest that a Vaccine strategy based on the stalk domain of the hemagglutinin protein could be used in humans to broadly protect against a variety of influenza Virus subtypes.