Abstract
Priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. To identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, DNA and live attenuated vaccines in ferrets. Live attenuated influenza A/Vietnam/1203/2004 (H5N1) candidate vaccine (LAIV, VN04 ca) primed ferrets efficiently while inactivated H5N1 vaccine could not prime the immune response in seronegative ferrets unless an adjuvant was used. However, the H5 HA DNA vaccine alone was as successful as an adjuvanted inactivated VN04 vaccine in priming the immune response to VN04 ca virus. The serum antibody titers of ferrets primed with H5 HA DNA followed by intranasal vaccination of VN04 ca virus were comparable to that induced by two doses of VN04 ca virus. Both LAIV-LAIV and DNA-LAIV vaccine regimens could induce antibody responses that cross-neutralized antigenically distinct H5N1 virus isolates including A/HongKong/213/2003 (HK03) and prevented nasal infection of HK03 vaccine virus. Thus, H5 HA DNA vaccination may offer an alternative option for pandemic preparedness.
Highlights
Influenza pandemics of varying severities have occurred in the last century
An unadjuvanted inactivated VN04 monovalent subvirion influenza vaccine was previously shown to be less immunogenic in humans and requires a vaccine dose of 90 mg of HA antigen in multiple doses to induce an antibody response similar to that of seasonal influenza vaccine [25,26]
Vaccination of ferrets with inactivated VN04 (iVN04) adjuvanted with TiterMax, a stable water-in-oil emulsion commonly used in animal studies, elicited serum neutralizing antibody titers (Nt Ab) response after the first dose and further increased to a titer of 190 following a boost with VN04 ca virus (Group 8)
Summary
Influenza pandemics of varying severities have occurred in the last century. The 1918 ‘‘Spanish flu’’ (H1N1) that claimed the lives of about 40 million people is perhaps one of the deadliest pandemics in history [1]. The 1957 ‘‘Asian flu’’ (H2N2) and the 1968 ‘‘Hong Kong flu’’ (H3N2) pandemics are believed to have been caused by viruses from reassortment of circulating human strains and avian viruses [2]. The recent emergence of the swineorigin influenza A H1N1 pandemic (pH1N1) virus is a sober reminder that viruses with novel antigenic properties can infect and spread among an immunologically naıve human population with potentially devastating consequences. Among the avian influenza viruses that have sporadically infected humans, highly pathogenic avian influenza (HPAI) H5N1 viruses pose the greatest threat due to their high virulence. There are concerns that H5N1 viruses could evolve and adapt to replicate and spread in the human population or gain human-tohuman transmissibility through reassortment with circulating human influenza A viruses [4]. The development of safe and efficacious vaccines against these viruses is a public health priority
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