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Effect of oligonucleotide adjuvant on the immune modulation induced by HIV-1
whole inactivated vaccine in antiretroviral naïve HIV-1 infected patients
Andrea Gori 1 , Daria Trabattoni 2 , Giuliano Rizzardini 3 , Renato Maserati 4 ,
Francesco Mazzotta 5 , Richard Bartholomew 7 , Georgia Theofan 7 , Dorothy H. Bray 8 ,
Mario Clerici 2
1
Institute of Infectious Diseases, and
2
Chair of Immunology, University of Milano, Milano,
3
Clinic of Infectious Diseases "L. Sacco" Hospital, Milano, Italy;
4
Department of Infectious Diseases, Ospedale San Matteo IRCCS, Pavia, Italy;
5
Department of Infectious Diseases, Ospedale SS Annunziata. Florence, Italy;
7
The Immune Response Corporation, Carlsbad, CA 92008, USA, and
8
Medical Research Council Clinical Trials Unit, London, UK.
Background
Synthetic oligonucleotides containing immunostimulatory cytosine-guanine (CpG)
dinucleotide motifs can enhance immune responses induced by vaccines. We examined
whether Remune ® (whole inactivated, gp120-depleted HIV-1 antigen in IFA),
co-formulated with a novel oligonucleotide immunostimulatory adjuvant, AmplivaxTM,
(IR103 therapeutic vaccine), can be safely administered in antiretroviral naïve HIVinfected
individuals. We also evaluated the effects of IR103 on immune system
parameters.
Methods
Thirty two antiretroviral naïve HIV-infected individuals previously enrolled in a 28 week
study of Remune ® vs. placebo were randomized into a rollover study to receive either
Remune ® (N=15) or IR103, Remune ® formulated with Amplivax (0.5 mg) (N=17) every
12 weeks for a total of 5 injections. Kinetics of changes in immune parameters are
evaluated at multiple times during the study period. Data from the ongoing study, obtained
at weeks 4 and 12 are presented herein.
Results
No safety issues were identified in any subjects through 12 weeks of evaluation. At week
12 (after 1 injection) compared to baseline the main immunological effect observed was a
skewing of the CD8 T cells towards the more mature, lytic subpopulations. Thus: 1) central
memory (CCR7+/RA-) CD8 T lymphocytes were diminished both in Remune ® and
IR103 groups; 2) effector memory (CCR7-/RA-) and terminally differentiated (CCR7-/RA+)
CD8 T cells were augmented both in Remune ® and IR103 subjects. These changes tend
to occur more rapidly in individuals receiving IR103 compared to Remune ® , as they are
already evident at week 4. In addition, the magnitude of these effects appears to be
greater in subjects receiving IR103 that had received Remune ® (vs. placebo) in the
previous study.
Conclusions
These preliminary results suggest that Amplivax, an oligonucleotide immunostimulatory
adjuvant, potentiates the immunomodulatory effects associated with Remune ® in antiretroviral
naïve HIV-infected individuals. Because defective maturation of CD8 T cells is one of the
main immunologic problems seen in HIV infection, these results could be of particular
interest in the management of HIV infected individuals. Further follow up data are
required to confirm these observations.
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