Current Status of Live Attenuated Influenza Vaccine in the United States for Seasonal and Pandemic Influenza

Christopher S. Ambrose; Catherine Luke; Kathleen Coelingh

Disclosures

Influenza Resp Viruses. 2008;2(6):193-202. 

In This Article

Live Attenuated Vaccines Against Pandemic Influenza

The emergence and spread of highly pathogenic avian influenza (HPAI) A/H5N1 viruses in avian populations since 2003 and the concurrent infections in humans have prompted efforts to develop vaccines for use in the event of an influenza pandemic. Most pandemic influenza vaccines currently licensed or in development target the H5N1 subtype and are inactivated injectable vaccines administered with or without adjuvant. It is important that every avenue for vaccine development be explored as part of pandemic preparedness activities. Live attenuated influenza vaccines against potential pandemic influenza A viruses are being developed in the United States and in Russia. Both approaches capitalize on the use of the technology and infrastructure already in place for seasonal LAIV, using MDVs that display ts, ca, and att phenotypes. Based on the experience with LAIV for seasonal influenza, it is reasonable to expect that potential advantages of using live attenuated vaccines against pandemic influenza include rapid induction of mucosal and systemic humoral and cell-mediated immune responses and broad cross-protection against antigenically distinct viruses.

In collaboration with MedImmune, the NIH (Bethesda, MD, USA), is engaged in a program to develop candidate pandemic LAIV (pLAIV) for use in the event of a pandemic. The candidate vaccines will be 6:2 reassortants, generated by reverse genetics, with the HA and NA genes of an influenza virus of pandemic potential, and the six internal protein genes of the cold-adapted MDV-A virus. The use of reverse genetics allows the removal of virulence motifs such as the multibasic cleavage site in the HA of HPAI viruses that is a known virulence factor in poultry.[47] The candidate vaccines will be thoroughly characterized in preclinical studies and evaluated for safety, infectivity, and immunogenicity in phase I clinical trials in healthy adults. Clinical studies are being conducted in inpatients at the Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA). The studies will establish the proof of principle of the utility of such vaccines in the event of an influenza pandemic.

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