Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1

Ascione, Alessandro; Capecchi, Barbara; Campitelli, Laura; Imperiale, Valentina; Flego, Michela; Zamboni, Silvia; Gellini, Mara; Alberini, Isabella; Pittiglio, Eliana; Donatelli, Isabella

doi:10.1016/j.antiviral.2009.05.005

Cited by 13 publications

(15 citation statements)

References 36 publications

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“…Several groups have used mouse passive transfer models to demonstrate the protective efficacy of monoclonal antibodies against lethal H5N1 virus challenge [30]–[40]. It is difficult to compare the majority of such studies with the present work since neutralizing antibody titers are not commonly reported.…”

Section: Discussionmentioning

confidence: 99%

“…Passive transfer has also been used to evaluate the protective efficacy of human gammaglobulin or human monoclonal antibodies against West Nile virus [24], [25], Ebola virus [26], [27], and Dengue Fever virus [28]. In addition, passive transfer of vaccine-induced immune sera between mice was used to demonstrate the protective efficacy of a licensed pandemic H1N1v vaccine [29], and several studies have revealed the potential of monoclonal antibodies to protect animals from lethal challenge with wild-type H5N1 virus [30]–[40]. To date, however, investigations into the efficacy of H5N1 vaccine-induced human immune sera to protect against lethal challenge with wild-type virus have not been reported.…”

Section: Introductionmentioning

confidence: 99%

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H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

et al. 2011

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BackgroundVero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge.MethodsWe used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus.ResultsPassive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species.ConclusionsThese data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

et al. 2011

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“…Other reporters such as lacZ (29,54,56,57) as well as Gaussia (58) and Renilla (59,60) luciferase are also used to a lesser extent.…”

Section: Reporter Systemsmentioning

confidence: 99%

Pseudotype-Based Neutralization Assays for Influenza: A Systematic Analysis

et al. 2015

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The use of vaccination against the influenza virus remains the most effective method of mitigating the significant morbidity and mortality caused by this virus. Antibodies elicited by currently licensed influenza vaccines are predominantly hemagglutination-inhibition (HI)-competent antibodies that target the globular head of hemagglutinin (HA) thus inhibiting influenza virus entry into target cells. These antibodies predominantly confer homosubtypic/strain specific protection and only rarely confer heterosubtypic protection. However, recent academia or pharma-led R&D toward the production of a “universal vaccine” has centered on the elicitation of antibodies directed against the stalk of the influenza HA that has been shown to confer broad protection across a range of different subtypes (H1–H16). The accurate and sensitive measurement of antibody responses elicited by these “next-generation” influenza vaccines is, however, hampered by the lack of sensitivity of the traditional influenza serological assays HI, single radial hemolysis, and microneutralization. Assays utilizing pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to be highly efficient for the measurement of homosubtypic and heterosubtypic broadly neutralizing antibodies, making them ideal serological tools for the study of cross-protective responses against multiple influenza subtypes with pandemic potential. In this review, we will analyze and compare literature involving the production of influenza pseudotypes with particular emphasis on their use in serum antibody neutralization assays. This will enable us to establish the parameters required for optimization and propose a consensus protocol to be employed for the further deployment of these assays in influenza vaccine immunogenicity studies.

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“…Both bavituximab, specific for phosphatidylserine, a phospholipid exposed on membranes of damaged cells, and MDX-1106, specific for PD-1, an inhibitory T cell costimulation receptor, have been used to control chronic hepatitis infection, particularly in the setting of HIV-coinfection [34,43]. The threat of a new pandemic makes influenza virus an important candidate for mAb development, with research currently being done to characterize human neutralizing antibodies and explore their therapeutic potential [24,44,45]. Historically, influenza virus has been extremely challenging because of its high antigenic variability.…”

Section: Viral Targetsmentioning

confidence: 99%

Monoclonal antibody-based therapies for microbial diseases

Saylor

Dadachova

Casadevall

2009

Vaccine

151

142

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The monoclonal antibody (mAb) revolution that currently provides many new options for the treatment of neoplastic and inflammatory diseases has largely bypassed the field of infectious diseases. Only one mAb is licensed for use against an infectious disease, although there are many in various stages of development. This situation is peculiar given that serum therapy was one of the first effective treatments for microbial diseases and that specific antibodies have numerous antimicrobial properties. The underdevelopment and underutilization of mAb therapies for microbial diseases has various complex explanations that include the current availability of antimicrobial drugs, small markets, high costs and microbial antigenic variation. However, there are signs that the climate for mAb therapeutics in infectious diseases is changing given increasing antibiotic drug resistance, the emergence of new pathogenic microbes for which no therapy is available, and development of mAb cocktail formulations. Currently, the major hurdle for the widespread introduction of mAb therapies for microbial diseases is economic, given the high costs of immunoglobulin preparations and relatively small markets. Despite these obstacles there are numerous opportunities for mAb development against microbial diseases and the development of radioimmunotherapy provides new options for enhancing the magic bullet. Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases.The field of infectious diseases has largely missed the monoclonal antibody (mAb) therapeutic revolution of the past decade. In contrast to such fields as oncology and rheumatology where mAbs have provided new effective therapies, only one mAb has been licensed for the treatment of an infectious disease [1]. This omission in the anti-infective armamentarium is particularly distressing given that the therapy of infectious disease is in crisis, since it is arguably the only field of medicine where effective intervention options have declined [2]. The crisis in infectious disease therapeutics is a consequence of four simultaneous developments, that in combination have significantly reduced treatment options for certain microbial diseases: 1) widespread antimicrobial drug resistance; 2) an epidemic of immunocompromised hosts in whom antimicrobial therapy is not as effective as in hosts with intact immunity; 3) the emergence of new pathogenic microbes for which no therapy exists; and 4) the re-emergence of older pathogenic microbes, often in drug-resistant form, as exemplified by multidrug-resistant (MDR) Mycobacterium tuberculosis.

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Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1

Cited by 13 publications

References 36 publications

H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

Pseudotype-Based Neutralization Assays for Influenza: A Systematic Analysis

Monoclonal antibody-based therapies for microbial diseases

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