scholarly journals Cross-Reactive Immunity to Clade 2 Strains of Influenza Virus A Subtype H5N1 Induced in Adults and Elderly Patients by Fluval, a Prototype Pandemic Influenza Virus Vaccine Derived by Reverse Genetics, Formulated with a Phosphate Adjuvant, and Directed to Clade 1 Strains

2008 ◽  
Vol 16 (4) ◽  
pp. 437-443 ◽  
Author(s):  
György Fazekas ◽  
Rita Martosne-Mendi ◽  
Istvan Jankovics ◽  
Istvan Szilvasy ◽  
Zoltan Vajo
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Reverse Genetics ◽  
Evolutionary Relationship ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Antigenic Structure ◽  
Elderly Subjects ◽  
H5n1 Influenza ◽  
Clade 1

ABSTRACT High fatality rates and multiple cases of transmission of avian H5N1 influenza viruses to humans illustrate the urgent need for an efficacious, cross-protective vaccine against H5N1 strains. Extensive genetic characterization of H5N1 strains has elucidated the natural evolutionary relationship of these strains, linking groups known as clades to a common ancestor. Although the clades and subclades probably differ sufficiently in their antigenic structure to warrant the preparation of different vaccines, there is some evidence that cross-reactive immunity can be afforded. We aimed to assess the immunogenicity of a clade 1 H5N1 (NIBRG-14) whole-virus vaccine with an aluminum phosphate adjuvant and to determine whether it can induce cross-reactive immunity against antigenically drifted clade 2 H5N1 strains, both those derived by reverse genetics and wild-type isolates. A total of 88 (44 adult and 44 elderly) subjects, who received one dose (6 μg) of the vaccine, were studied. As judged by U.S. and European licensing criteria based on hemagglutination inhibition, the subjects developed cross-reactive immunity against all studied H5N1 strains belonging to a clade different from that of the strain utilized to produce the vaccine. Our findings highlight the importance of stockpiling, since cross-immune reactions induced by prepandemic vaccines will likely reduce morbidity and mortality in case of a pandemic.

scholarly journals Influenza reverse genetics: dissecting immunity and pathogenesis

2014 ◽  
Vol 16 ◽  
Author(s):  
Siying Ye ◽  
Justin G. Evans ◽  
John Stambas
Keyword(s):  
Influenza Virus ◽  
Protein Function ◽  
Reverse Genetics ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Host Pathogen Interactions ◽  
H5n1 Influenza ◽  
Host Pathogen ◽  
Cloned Cdna ◽  
Novel Therapeutic Strategies

Reverse genetics systems allow artificial generation of non-segmented and segmented negative-sense RNA viruses, like influenza viruses, entirely from cloned cDNA. Since the introduction of reverse genetics systems over a decade ago, the ability to generate ‘designer’ influenza viruses in the laboratory has advanced both basic and applied research, providing a powerful tool to investigate and characterise host–pathogen interactions and advance the development of novel therapeutic strategies. The list of applications for reverse genetics has expanded vastly in recent years. In this review, we discuss the development and implications of this technique, including the recent controversy surrounding the generation of a transmissible H5N1 influenza virus. We will focus on research involving the identification of viral protein function, development of live-attenuated influenza virus vaccines, host–pathogen interactions, immunity and the generation of recombinant influenza virus vaccine vectors for the prevention and treatment of infectious diseases and cancer.

scholarly journals Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children

2008 ◽  
Vol 15 (7) ◽  
pp. 1042-1053 ◽  
Author(s):  
Bruce D. Forrest ◽  
Michael W. Pride ◽  
Andrew J. Dunning ◽  
Maria Rosario Z. Capeding ◽  
Tawee Chotpitayasunondh ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Young Children ◽  
Immune Responses ◽  
Virus Vaccine ◽  
Elispot Assay ◽  
Influenza Virus Vaccine ◽  
The Philippines ◽  
Influenza Viruses ◽  
Ifn Γ

ABSTRACT The highly sensitive gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-γ ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months, an intranasal dose of 107 fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination. The role of CMI in actual protection against community-acquired, culture-confirmed clinical influenza by CAIV-T was investigated in a large randomized, double-blind, placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to <36 months in the Philippines and Thailand. The estimated protection curve indicated that the majority of infants and young children with ≥100 spot-forming cells/106 peripheral blood mononuclear cells were protected against clinical influenza, establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN-γ is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza, especially those used for children.

scholarly journals Analysis of the efficacy of an adjuvant-based inactivated pandemic H5N1 influenza virus vaccine

2019 ◽  
Vol 164 (4) ◽  
pp. 1027-1036 ◽  
Author(s):  
Ainur Nurpeisova ◽  
Markhabat Kassenov ◽  
Nurkuisa Rametov ◽  
Kaissar Tabynov ◽  
Gourapura J. Renukaradhya ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Influenza Virus Vaccine ◽  
H5n1 Influenza Virus ◽  
H5n1 Influenza

Responses of Elderly Subjects to a New Submit Influenza Virus Vaccine

1982 ◽  
Vol 145 (2) ◽  
pp. 277-277 ◽  
Author(s):  
M. W. Brandriss ◽  
J. J. Schlesinger ◽  
R. G. Douglas
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Influenza Virus Vaccine ◽  
Elderly Subjects

scholarly journals Immunity to influenza in ferrets: VII. Effect of previous infection with heterotypic and heterologous influenza viruses on the response of ferrets to inactivated influenza virus vaccines

1974 ◽  
Vol 72 (1) ◽  
pp. 91-100 ◽  
Author(s):  
C. McLaren ◽  
C. W. Potter
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Virus Vaccine ◽  
Serum Antibody ◽  
Influenza Virus Vaccine ◽  
Challenge Infection ◽  
Influenza Viruses ◽  
Subsequent Challenge ◽  
Ann Arbor ◽  
Previous Infection

SUMMARYNormal ferrets did not produce serum antibody following immunization with 200 i.u. of inactivated A/Hong Kong/68 influenza virus vaccine and were found to be susceptible to subsequent challenge infection with A/Hong Kong/68 virus. High titres of virus were recovered from nasal washings collected 3 days after infection, serum antibody was produced, increased nasal protein was detected and HI antibody was detected in nasal washings. Ferrets infected with influenza virus A/PR/8/34 7 weeks before immunization with inactivated A/HK/68 virus did, however, produce serum HI antibody to A/HK/68 virus. This antibody conferred partial immunity to challenge infection with A/HK/68 virus, as shown by decreased titres of virus in nasal washings and reduced levels of nasal protein. Previous infection of ferrets with influenza virus B/Ann Arbor/66 did not result in the production of serum antibody to A/HK/68 virus following immunization with A/HK/68 vaccine and the animals were completely susceptible to subsequent challenge infection with A/HK/68 virus. Differences in the amount of nasal protein and nasal antibody produced after A/HK/68 infection were also found in ferrets previously infected with either A/PR/8/34 or B/AA/66 virus, compared with normal ferrets.

scholarly journals Broadly Neutralizing Anti-Influenza Virus Antibodies: Enhancement of Neutralizing Potency in Polyclonal Mixtures and IgA Backbones

2015 ◽  
Vol 89 (7) ◽  
pp. 3610-3618 ◽  
Author(s):  
Wenqian He ◽  
Caitlin E. Mullarkey ◽  
J. Andrew Duty ◽  
Thomas M. Moran ◽  
Peter Palese ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Virus Vaccine ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Human Peripheral Blood ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Broadly Neutralizing Antibodies ◽  
Variable Regions

ABSTRACTCurrent influenza virus vaccines rely upon the accurate prediction of circulating virus strains months in advance of the actual influenza season in order to allow time for vaccine manufacture. Unfortunately, mismatches occur frequently, and even when perfect matches are achieved, suboptimal vaccine efficacy leaves several high-risk populations vulnerable to infection. However, the recent discovery of broadly neutralizing antibodies that target the hemagglutinin (HA) stalk domain has renewed hope that the development of “universal” influenza virus vaccines may be within reach. Here, we examine the functions of influenza A virus hemagglutinin stalk-binding antibodies in an endogenous setting, i.e., as polyclonal preparations isolated from human sera. Relative to monoclonal antibodies that bind to the HA head domain, the neutralization potency of monoclonal stalk-binding antibodies was vastly inferiorin vitrobut was enhanced by several orders of magnitude in the polyclonal context. Furthermore, we demonstrated a surprising enhancement in IgA-mediated HA stalk neutralization relative to that achieved by antibodies of IgG isotypes. Mechanistically, this could be explained in two ways. Identical variable regions consistently neutralized virus more potently when in an IgA backbone compared to an IgG backbone. In addition, HA-specific memory B cells isolated from human peripheral blood were more likely to be stalk specific when secreting antibodies of IgA isotypes compared to those secreting IgG. Taken together, our data provide strong evidence that HA stalk-binding antibodies perform optimally when in a polyclonal context and that the targeted elicitation of HA stalk-specific IgA should be an important consideration during “universal” influenza virus vaccine design.IMPORTANCEInfluenza viruses remain one of the most worrisome global public health threats due to their capacity to cause pandemics. While seasonal vaccines fail to protect against the emergence of pandemic strains, a new class of broadly neutralizing antibodies has been recently discovered and may be the key to developing a “universal” influenza virus vaccine. While much has been learned about the biology of these antibodies, most studies have focused only on monoclonal antibodies of IgG subtypes. However, the study of monoclonal antibodies often fails to capture the complexity of antibody functions that occur during natural polyclonal responses. Here, we provide the first detailed analyses of the biological activity of these antibodies in polyclonal contexts, comparing both IgG and IgA isotypes isolated from human donors. The striking differences observed in the functional properties of broadly neutralizing antibodies in polyclonal contexts will be essential for guiding design of “universal” influenza virus vaccines and therapeutics.

scholarly journals Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raveen Rathnasinghe ◽  
Mirella Salvatore ◽  
Hongyong Zheng ◽  
Sonia Jangra ◽  
Thomas Kehrer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Type I ◽  
Respiratory Pathogens ◽  
Structural Protein ◽  
Human Influenza Virus

AbstractThe influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

scholarly journals Universal influenza virus neuraminidase vaccine elicits protective immune responses against human seasonal and pre-pandemic strains

2021 ◽  
Author(s):  
Amanda L. Skarlupka ◽  
Anne Gaelle Bebin-Blackwell ◽  
Spencer F. Sumner ◽  
Ted M. Ross
Keyword(s):  
North Carolina ◽  
Influenza Virus ◽  
Vaccine Development ◽  
Surface Protein ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Vaccine Antigen ◽  
Viet Nam ◽  
H5n1 Influenza

The hemagglutinin (HA) surface protein is the primary immune target for most influenza vaccines. The neuraminidase (NA) surface protein is often a secondary target for vaccine designs. In this study, computationally optimized broadly reactive antigen methodology was used to generate the N1-I NA vaccine antigen that was designed to cross-react with avian, swine, and human influenza viruses of N1 NA subtype. The elicited antibodies bound to NA proteins derived from A/California/07/2009 (H1N1)pdm09, A/Brisbane/59/2007 (H1N1), A/Swine/North Carolina/154074/2015 (H1N1) and A/Viet Nam/1203/2004 (H5N1) influenza viruses, with NA-neutralizing activity against a broad panel of HXN1 influenza strains. Mice vaccinated with the N1-I COBRA NA vaccine were protected from mortality and viral lung titers were lower when challenged with four different viral challenges: A/California/07/2009, A/Brisbane/59/2007, A/Swine/North Carolina/154074/2015 and A/Viet Nam/1203/2004. Vaccinated mice had little to no weight loss against both homologous, but also cross-NA genetic clade challenges. Lung viral titers were lower compared to the mock vaccinated mice, and at times, equivalent to the homologous control. Thus, the N1-I COBRA NA antigen has the potential to be a complimentary component in a multi-antigen universal influenza virus vaccine formulation that also contains HA antigens. Importance The development and distribution of a universal influenza vaccines would alleviate global economic and public health stress from annual influenza virus outbreaks. The influenza virus NA vaccine antigen allows for protection from multiple HA subtypes and virus host origins, but it has not been the focus of vaccine development. The N1-I NA antigen described here protected mice from direct challenge of four distinct influenza viruses and inhibited the enzymatic activity of a N1 influenza virus panel. The use of the NA antigen in combination with the HA widens the breadth of protection against various virus strains. Therefore, this research opens the door to the development of a longer lasting vaccine with increased protective breadth.

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