AIDSWEEKLY Plus, Monday, 2 June 1997
Daniel J. DeNoon, Senior Editor
Cellular immune responses to AIDS vaccines are effective against all of the many HIV subtypes.
The good news comes from two different research groups reporting at the 9th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held May 4-7, 1997, in Bethesda, Maryland.
Most people with HIV infection in North America and western Europe carry clade B HIV-1. Nearly all AIDS vaccine research employs candidate vaccines based on clade B viruses (see related HIV screening story in this issue).
But most people with HIV infection in Africa and Asia - where an AIDS vaccine is most urgently needed - are infected with non-B HIV-1 clades. Would a clade B vaccine be of any use?
The surprising answer is that it would.
"I think a B-clade vaccine will elicit responses that will be effective in Uganda," said Frances Gotch of Chelsea & Westminster Hospital, London.
"A vaccine based on a single clade could induce effective cross-reactive cellular immunity," said Huyen Cao of Massachusetts General Hospital, Boston.
This optimism is based on the growing consensus that an effective AIDS vaccine will have to elicit HIV specific cellular immune responses, particularly cytotoxic lymphocytes (CTLs). The studies by Gotch et al. and Cao et al. showed that unlike epitopes that elicit neutralizing antibodies, epitopes that elicit CTL responses are well conserved across HIV-1 subtypes.
At their research facility in Entebbe, Uganda, Gotch and coworkers obtained CTLs from asymptomatic donors with HIV infection. Clades A and D were most prevalent, with some donors carrying clade C virus. From the U.K. the researchers also obtained CTLs from donors infected with clade B virus.
The researchers then used a vaccinia-gag construct to express HIV-1 Gag proteins from clades B, A1, A2, C, and D in target cells.
CTLs from both the Ugandan and U.K. patients recognized most of the target cells, even though tissue typing showed that the two populations differed widely in expression of HLA- A and HLA-B alleles.
"Most patients can make cross-reactive responses to Gag," Gotch said.
Cao and colleagues evaluated CTL responses in 14 African subjects infected with clade A, C, or G virus. All were able to recognize target cells pulsed with clade B virus constructs.
They then showed that U.S. patients infected with clade B virus had CTL responses that cross-reacted with non-B clade epitopes.
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