Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
The H5N1 highly pathogenic avian influenza virus has been circulating in poultry in Asia, the Middle East, and Africa since its first appearance in southern China in 1996. This virus occasionally infects humans with a high case mortality rate and poses a significant pandemic threat. Since neutralizing antibodies generally play a major role in protective immunity against influenza viruses, antibody therapy is a potential option for preventing highly lethal infection with the H5N1 virus in humans. Here we evaluated the protective potential of a human-mouse chimeric monoclonal antibody with strong neutralizing activity against H5N1 viruses in mouse and nonhuman primate models of lethal H5N1 virus infection. The therapeutic use of the neutralizing antibody resulted in reduced viral loads and improved survival in animals infected with highly pathogenic H5N1 viruses. It was noted that the protective effects were more prominent in immunosuppressed macaques, which might provide a model of protection against severe clinical disease in immunocompromised patients. In addition, combination therapy together with an antiviral drug reduced the selection of escape mutants. Collectively, this study suggests that antibody therapy may have beneficial effects in clinical cases of H5N1 HPAI virus infection in humans.
Vyšlo v časopise:
Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004192
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004192
Souhrn
The H5N1 highly pathogenic avian influenza virus has been circulating in poultry in Asia, the Middle East, and Africa since its first appearance in southern China in 1996. This virus occasionally infects humans with a high case mortality rate and poses a significant pandemic threat. Since neutralizing antibodies generally play a major role in protective immunity against influenza viruses, antibody therapy is a potential option for preventing highly lethal infection with the H5N1 virus in humans. Here we evaluated the protective potential of a human-mouse chimeric monoclonal antibody with strong neutralizing activity against H5N1 viruses in mouse and nonhuman primate models of lethal H5N1 virus infection. The therapeutic use of the neutralizing antibody resulted in reduced viral loads and improved survival in animals infected with highly pathogenic H5N1 viruses. It was noted that the protective effects were more prominent in immunosuppressed macaques, which might provide a model of protection against severe clinical disease in immunocompromised patients. In addition, combination therapy together with an antiviral drug reduced the selection of escape mutants. Collectively, this study suggests that antibody therapy may have beneficial effects in clinical cases of H5N1 HPAI virus infection in humans.
Zdroje
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Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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