Important note: Information in this article was accurate in June 2003. The state of the art June have changed since the publication date. |
AIDSWEEKLY Plus; Monday, June 16, 2003
Michael Greer, Senior Medical Writer
"Cellular immune responses, particularly those associated with CD3+ CD8+ cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1)," according to Danilo R. Casimiro and colleagues working at Merck Research Laboratories in West Point, Pennsylvania.
An adenovirus vector expressing the HIV gag gene produced robust anti-Gag T-cell responses in rhesus macaques, especially after priming with an adjuvanted DNA vaccine, Casimiro and coauthors found.
The researchers assessed the efficacy of a modified vaccinia virus Ankara vector, a replication-defective adenovirus serotype 5 (Ad5) vector, and a number of DNA plasmid vaccines with or without adjuvants. All of the vaccine formulations tested expressed an identical codon-optimized gag gene, they noted.
The most potent Gag-specific cytotoxic T lymphocyte (CTL) responses were seen in macaques immunized with the Ad5-gag vaccine, study data showed. Priming animals with a DNA vaccine augmented cellular immune activity induced with the Ad5 vector.
A DNA vaccine formulated with the adjuvant CRL1005 provided the most effective priming (Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene. J Virol. 2003 Jun;77(11):6305-13.
"These results are suggestive of an immunization strategy for humans that are centered on use of the adenovirus vector and in which existing adenovirus immunity may be overcome by combined immunization with adjuvanted DNA and adenovirus vector boosting," Casimiro and collegues concluded.
The corresponding author for this report is Danilo R. Casimiro, Department of Viral Vaccine Research, Merck & Co., WP26-145, 770 Sumneytown Pike, West Point, PA 19486, USA. E-mail: danilo_casimiro@merck.com.
Key points reported in this study include:
An HIV Gag-expressing adenovirus vector elicits powerful cellular immune responses in rhesus macaques
Priming with a DNA vaccine enhanced these responses
Optimal results were achieved when the prime vaccine was adjuvanted with CRL1005
This article was prepared by AIDS Weekly editors from staff and other reports.
Reference
Casimiro DR, Chen L, Fu TM, et al., "Comparative Immunogenicity in Rhesus Monkeys of DNA Plasmid, Recombinant Vaccinia Virus, and Replication-Defective Adenovirus Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene", J Virol. 2003 Jun;77(11):6305-13.
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