From the 12th Colloquium of the Cent Gardes, Marnes-la-Coquette, France, 25-27 October
Norman Letvin (Harvard Medical School) gets the party pooper prize at this year’s Paris summit: “No one has yet presented compelling evidence that the immune system will be successful by itself in the absence of therapy. It is a seductive idea, but just because it is intuitively comfortable does not necessarily mean it will be borne out in fact.”
Frances Gotch (Chelsea and Westminster Hospital, London) presented preliminary results from her 60-patient HAART +/- Remune +/- IL-2 study. Although she reported anti-HIV T helper responses “as strong as or stronger than those in long-term nonprogressors,” these Remune induced responses have not yet been shown to result in improved immune control of HIV.
Merck has apparently begun immunizing volunteers in its first HIV vaccine trial. Merck officials say that if their vaccine is shown capable of generating potent cellular immune responses in HIV-negative volunteers, they will move quickly to study it in HIV-positive individuals.
Glaxo Wellcome is reportedly planning a Phase I study of a “therapeutic” HIV vaccine. The company is working with a U.K. based company which develops preventive and therapeutic vaccines using a gene gun delivery system.
Alessandro Gringeri (Maggiore Hospital, Italy) has conducted a Phase II trial of tat toxoid in HIV-infected individuals.The study, according to Daniel Zagury (Université Pierre et Marie Curie, Paris), showed that tat toxoid is safe, well-tolerated and capable of raising antibodies to tat (Gringeri A et al. Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients. Hum Virol 1998 May-Jun;1(4):293-8, see also, Zagury JF et al. Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine. Hum Virol 1998 May-Jun;1(4):282-92).
Results of a monkey study with Zagury’s tat toxoid vaccine, according to David Pouza (University of Wisconsin), showed little difference between the treated animals and the controls — although Pouza speculated that such a tat vaccine could attenuate disease in monkeys.
Barbara Ensoli (Instituto Superiore di Sanita, Rome) presented data on two different tat based approaches: an SIV tat protein and an SIV tat DNA. Since her tat protein study was published in a recent issue of Nature Medicine (Cafaro A et al. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med 1999 Jun;5(6):643-50), Ensoli focused on her tat DNA vaccine data at the Cent Gardes meeting. After SHIV challenge, four monkeys immunized intramuscularly had no detectable viremia and normal CD4 levels — compared to high levels of virus in the control animals. Criticism of Ensoli’s work centered around the relatively non-pathogenic nature of the SHIV challenge virus.
In an attempt to create exposed but unifected monkeys, Ron Desrosiers (New England Primate Research Center, Boston) administered a highly attenuated SIV strain via low-dose, escalating rectal immunizations. These monkeys (unlike those immunized intramuscularly) did not develop measurable SIV antibodies, although they did have SIV-specific lymphoproliferative responses. When a more sensitive test was employed, some evidence of SIV antibodies was detected. Desroisers plans to challenge these animals soon. He also plans to use this new ultra-sensitive antibody test in exposed but seronegative humans.
Michael Klein (Pasteur Merieux Connaught, the sponsor of the meeting) concluded his review of PMC’s vaccine program with the sobering remarks, “There is reason for optimism, but even if we had an AIDS vaccine, it would take ten years to get in on the market and to the world.” PMC will also initiate a therapeutic vaccine trial shortly: poxvirus vectors associated with either gp160 subunits or lipopeptides — with or without IL-2.
Selected Primate Models of HIV Infection
|Virus||Viral replication||Disease manifestation|
|SIVsm PBj14||high||<1 yr progression to AIDS|
|SHIV KU2||high||1-2 yr progression to AIDS|
|SIVmac239||high||2 yr progression to AIDS|
|SIVmac251||high||2 yr progression to AIDS|
|SHIV 89.6P||high||2 yr progression to AIDS|
|SIVsmE660||high||3 yr progression to AIDS|
|HIV-1 JC||high||high viremia, rapid CD4 decline|
|HIV-1 DH12||high||persistent infection; no disease|
|HIV-1 5016||high||persistent infection; no disease|
|HIV-1 LAI||med||persistent infection; no disease|
|HIV-1 SF2||low||transient infection|