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The development of an H2N2 vaccine is a priority in pandemic preparedness planning. We previously showed that a single dose of a cold-adapted (ca) H2N2 live attenuated influenza vaccine (LAIV) based on the influenza A/Ann Arbor/6/60 (AA ca) virus was immunogenic and efficacious in mice and ferrets. However, in a Phase I clinical trial, viral replication was restricted and immunogenicity was poor....
H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV).Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04...
CIA05 is a toll-like receptor (TLR) 4 agonist derived from an Escherichia coli lipopolysaccharide (LPS) mutant and has been shown to have potential as a vaccine adjuvant. In this study, we investigated the immunopotentiating activity of the adjuvant system CIA06, which is comprised of CIA05 and aluminum hydroxide (alum), when used with the human papillomavirus (HPV) L1 virus-like particles (VLPs)...
A miniaturized neuraminidase inhibition (NI) assay using HA-mismatched H6 reassortant viruses was performed to examine the neuraminidase (NA)-specific antibody response in ferrets immunized with live-attenuated influenza vaccine (LAIV) strains. The strains tested possessed different NAs derived from seasonal H1N1 and H3N2, 2009 pandemic H1N1, and the highly pathogenic influenza H5N1 virus. The anti-NA...
The proteolytic enzyme bromelain has been traditionally used to cleave the hemagglutinin (HA) protein at the C-terminus of the HA2 region to release the HA proteins from influenza virions. The bromelain cleaved HA (BHA) has been routinely used as an antigen to generate antiserum that is essential for influenza vaccine product release. The HA of the 2009 pandemic H1N1 influenza A/California/7/2009...
We describe the results of an open label Phase I trial of a live attenuated H6N1 influenza virus vaccine (ClinicalTrials.gov Identifier: NCT00734175).We evaluated the safety, infectivity, and immunogenicity of two doses of 10 7 TCID 50 of the H6N1 Teal HK 97/AA ca vaccine, a cold-adapted and temperature sensitive live, attenuated influenza vaccine (LAIV) in healthy seronegative adults...
Influenza H3N2 viruses have recently drifted from A/Wisconsin/67/05-like to A/Brisbane/10/07-like viruses. The effect of key amino acid substitutions in the hemagglutinin (HA) protein on the replication, antigenicity and immunogenicity of cold-adapted, live attenuated vaccine strains was examined. A/Brisbane/10/07 egg isolate contained a unique combination of G186 and P194 which were required for...
Development of live attenuated influenza vaccines (LAIV) against avian viruses with pandemic potential is an important public health strategy.We performed open-label trials to evaluate the safety, infectivity, and immunogenicity of H5N1 VN 2004 AA ca and H5N1 HK 2003 AA ca. Each of these vaccines contains a modified H5 hemagglutinin and unmodified N1 neuraminidase from the respective wild-type (wt)...
Live attenuated influenza vaccines (LAIVs) are being developed and tested against a variety of influenza viruses with pandemic potential. We describe the results of an open-label Phase I trial of a live attenuated H7N3 virus vaccine.The H7N3 BC 2004/AA ca virus is a live attenuated, cold-adapted, temperature-sensitive influenza virus derived by reverse genetics from the wild-type low pathogenicity...
The currently circulating influenza B viruses from both antigenic lineages contain an N-linked glycosylation site in the hemagglutinin (HA) protein at positions of 196 or 197. However, egg adaptation caused the loss of the glycosylation site that could impact virus antigenicity and vaccine efficacy. The effect of the 196/197 glycosylation site on influenza B virus growth and antigenicity was systemically...
Most of the recently circulating H3N2 influenza A strains do not replicate well in embryonated chicken eggs and had to be isolated by cell culture, which presents a great challenge for influenza vaccine production using embryonated chicken eggs. We previously reported that a human H3N2 virus, A/Fujian/411/02, which replicates poorly in eggs, could be improved by changing a minimum of two HA residues...
Towards the goal of developing live attenuated respiratory syncytial virus (RSV) vaccines to prevent severe respiratory tract infections caused by respiratory syncytial virus, recombinant RSV containing a deletion of single or multiple NS1, NS2, SH and M2-2 genes have been generated. In this study, recombinants, rA2ΔM2-2, rA2ΔNS2, rA2ΔNS1NS2, rA2ΔSHNS2, rA2ΔM2-2NS2 were evaluated in African green...
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