A virus that shows promise as a means of vaccine delivery of HIV-1 antigens could be altered to become effective in a larger portion of the population according to research published online by Nature this week.
Adenovirus serotype 5 (Ad5) vectors carrying HIV-1 antigens have been shown to generate high immune responses in preclinical studies and are therefore being developed as candidate AIDS vaccines. A problem facing researchers is that a large majority of the human population has pre-existing Ad5-specific neutralizing antibodies that could reduce the effectiveness of this particular vaccine vector.
Knowing that many Ad5-specific antibodies target the outer capsid hexon protein, Dan Barouch and colleagues swapped the surface loops - hypervariable regions - with the corresponding hypervariable regions from another adenovirus with lower pre-existing immunity in humans.
They found that these chimaeric carriers were stable and effectively evaded pre-existing anti-Ad5 immunity in both mice and rhesus monkeys. Furthermore, a high immune response was generated against the encoded vaccine antigen: the Gag protein from simian immunodeficiency virus. These engineered vaccine vectors could provide a major advance for the fields of vaccination and gene therapy.
Dan H. Barouch (Harvard Medical School, Boston, MA, USA)
Abstract available online.
(C) Nature press release.
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