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A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection

tetano

Editor, Senior Moderator
J Infect Dis. 2012 Mar 23. [Epub ahead of print]
A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection.
Giles BM, Crevar CJ, Carter DM, Bissel SJ, Schultz-Cherry S, Wiley CA, Ross TM.
Source

Center for Vaccine Research.
Abstract

BackgroundHighly pathogenic H5N1 avian influenza viruses continue to spread via waterfowl causing lethal infections in humans. Vaccines can prevent the morbidity and mortality associated with pandemic influenza isolates. Predicting the specific isolate that may emerge from the 10 different H5N1 clades is a tremendous challenge for vaccine design.MethodsIn this study, we generated a synthetic hemagglutinin (HA) based upon a new methodology, computationally optimized broadly reactive antigen (COBRA), which utilizes worldwide sequencing and surveillance efforts that are specifically focused on sequences from H5N1 clade 2 human isolates.ResultsCynomolgus macaques vaccinated with COBRA clade 2 HA H5N1 virus-like particles (VLP) had hemagglutination-inhibition antibody titers that recognized a broader number of representative isolates from divergent clades compared to non-human primates vaccinated with a clade 2.2 HA VLP. Furthermore, all vaccinated animals were protected from A/Whooper Swan/Mongolia/244/2005 (WS/05) clade 2.2 challenge with no virus detected in the nasal or tracheal washes. However, COBRA VLP vaccinated non-human primates had reduced lung inflammation and pathology compared to WS/05 VLP vaccines.ConclusionThe COBRA clade 2 HA H5N1 VLP elicits broad humoral immunity against multiple H5N1 isolates from different clades. In addition, the COBRA VLP vaccine more effective against a HPAI virus challenge than a homologous vaccine.

PMID:
22448011
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22448011
 
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