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HOME > Osong Public Health Res Perspect > Volume 2(Suppl 1); 2011 > Article
Articles Strategies for Control of Pandemic Influenza: Active and Passive Immunization
Huan H. Nguyen
Osong Public Health and Research Perspectives 2011;2(Suppl 1):S5-S6.
DOI: https://doi.org/10.1016/j.phrp.2011.11.023
Published online: November 30, 2011
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Head of the Viral Immunology Section, International Vaccine Institute, Seoul, Korea

Copyright ©2012, Korea Centers for Disease Control and Prevention

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License () which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Pandemic influenza poses a serious threat to global health and the world economy. Highly pathogenic avian influenza A virus (HPAIV) of the H5N1 subtype that has emerged since 2004, resulted in more than 430 cases in 15 countries with a 50% case-fatality rate. Novel vaccine strategies for early response include the use of attenuated vaccines/vectors administered via novel mucosal immunization routes, therapeutic anti-virals and passive immunization with virus-specific antibodies (Abs).
The current influenza vaccines designed for inducing antibody (Ab) responses against viral surface antigens (i.e., hemagglutinin [HA] and neuraminidase [NA]) are limited to seasonal use because of the ability of the virus to mutate these major antigenic glycoproteins. Vaccines that target determinants conserved among influenza A viruses (IAV) to generate broad protection against infection with different influenza A subtypes (i.e., heterosubtypic immunity [HSI]) remain elusive. We have currently developed a recombinant adenovirus (Ad) vector co-encoding HA (H5 subtype) and a conserved ectodomain of matrix protein 2 (M2e) (AdH5/M2e) for induction of protective immunity to H5N1 and other subtypes. Another approach based on the use of influenza virus carrying a deletion in the nonstructural NS1 gene is being explored. Since NS1 enables the virus to disarm the host type 1 IFN response, such deletion leads to attenuation of the viruses and enhanced host antiviral response. Therefore, vaccines based on NS1 deleted viruses (DelNS1) may provide better protection than inactivated vaccines and could induce HSI to infection with different influenza virus A subtypes. Sub-lingual immunization has been found to be a safe and effective route for induction of protective immune responses in systemic and mucosal compartments including respiratory tract. We found that sublingual immunization with either AdH5/M2e or DelNS1 induces broad protective immunity to H5 viruses and other influenza virus A subtypes including H1N1.
Passive immunization (the transfer of specific immunoglobulins/Abs to a previously nonimmune recipient host) could offer an alternative strategy to prevent and treat influenza virus infection and an additional therapeutic option to antiviral drugs that are limited by widespread drug resistance among influenza virus strains. Even after targeted vaccines become available, passive immunization could still have prophylactic effects and provides an additional countermeasure against influenza, especially for individuals who do not respond well to the vaccines. Attempts to develop monoclonal Abs (mAbs) have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV) strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We found that eggs obtained from chicken farms and supermarkets in Vietnam contain H5N1-specific immunoglobulins (IgY) that provide protection against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection with HPAIV H5N1, H5N1-specific IgY prevent disease or significantly reduce viral replication resulting in complete recovery from the disease, respectively. In addition, we generated H1N1 virusspecific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection.
These results underscore the usefulness of recombinant Ad vectors encoding surface glycoprotein (HA) and conserved protein (M2e) and NS1 deleted viruses (DelNS1) as vaccine candidates for control of pre-pandemic H5N1 and newly emerging subtypes. Data on antiviral efficacy of IgY provide a proof-of-concept for the approach using virus-specific IgY as affordable, safe, and effective alternative for the control of influenza outbreaks, including the potential H5N1 and current H1N1 pandemic.

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