Progress reported in HIV vaccine development
Rewind to 1997: President Clinton announces a 10-year goal for the development of an HIV/ AIDS vaccine. Fast forward to 2007. Are you able to provide such a vaccine to your patients?
While no vaccine has yet been cleared by the Food and Drug Administration, progress has been made in developing potential candidates. Just-published research reports results from two candidate vaccines that eventually may be used together to confer immunity against HIV infection.1,2
"These two trials represent the progression of novel vaccines based on adenovirus vectors through the initial safety studies in humans," observes Harriet Robinson, PhD, chief of microbiology and immunology at Emory University's Yerkes Research Center in Atlanta. "Other vectors, in particular poxvirus vectors, are also moving through safety studies in humans."
Clinical studies with these candidate vaccines will require five to seven more years, estimates Robinson, co-author of an editorial commentary on the recent research.3 However, the field is moving toward an HIV/AIDS vaccine, she states.
Such development is important; most U.S. adults believe that HIV vaccines represent the best hope for controlling the global AIDS epidemic.4 More than 40 million people are now living with HIV/AIDS; three million deaths occur annually because of HIV/AIDS infection.5
Look at response
In the recently published research, scientists with the National Institutes of Health Vaccine Research Center in Bethesda, MD, the Fred Hutchinson Cancer Research Center in Seattle, and GenVec in Gaithersburg, MD, examined the use of the two vaccine candidates in healthy, uninfected adults. The first candidate was a plasmid DNA-based vaccine expressing genes from three dominant HIV subtypes,1 and the second used recombinant adenovirus serotype 5 (rAd5) as a vector to deliver similar HIV strains.2 Fifty men and women were included in the DNA vaccine trial,1 while 36 men and women were entered in the recombinant vector vaccine trial.2
Researchers report 97.5% of those vaccinated with the DNA vaccine experienced positive CD4 T cell responses and 40% experienced positive CD8 T cell responses by week 12 following immunization.1 In the case of the recombinant vector vaccine, 93.3% of those vaccinated experienced positive CD4 T cell responses, and 60% experienced positive CD8 T cell responses by week four following immunization. While the recombinant vector vaccine was well-tolerated, higher doses led to some adverse events such as pain and fever, the scientists note.2
Both of the candidate vaccines operate by gene delivery of customized vaccine antigens produced by host cells to initiate an immune response. While the DNA vaccine approach does not have the problem of anti-vector immunity, it may be less potent than vector-based gene delivery strategies, observes Barney Graham, MD, PhD, director of clinical studies at the Vaccine Research Center. Replication-defective rAd5 offers targeted, efficient gene delivery and high potency, but it also may be susceptible to anti-vector immunity, notes Graham, who serves as lead author of the DNA vaccine study.
Scientists are looking at combining the two vaccine strategies for an even more effective vaccine product, says Graham. Such an approach will use the DNA vaccine candidate to prime the immune response and a replication defective recombinant adenovirus serotype 5 vector to boost responses. Researchers are using a new 6-plasmid product in current studies, with an additional boost given at six months with the adenovirus product, says Graham.
By using the DNA vaccine, combined with the adenovirus delivery of these genes that broadly cover many of the important strains of HIV, early research indicates even better immune responses than either modality alone, reports Graham. "Our big plans are to ask whether these products in combination, which have even better immune responses than either product alone, will make good enough immune responses to reduce HIV infection or reduce disease progression from HIV," he states.
References
- Graham BS, Koup RA, Roederer M, et al. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis 2006; 194:1,650-1,660.
- Catanzaro AT, Koup RA, Roederer M, et al. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector. J Infect Dis 2006; 194:1,638-1,649.
- Robinson HL, Weinhold KJ. Phase 1 clinical trials of the National Institutes of Health Vaccine Research Center HIV/AIDS candidate vaccines. J Infect Dis 2006; 194:1,625-1,627.
- Allen MA, Liang TS, La Salvia T, et al. Assessing the attitudes, knowledge, and awareness of HIV vaccine research among adults in the United States. J Acquir Immune Defic Syndr 2005; 40:617-624.
- UNAIDS/WHO. AIDS Epidemic Update: December 2005. Geneva: UNAIDS, 2005.
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