Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption.
The safety and immunogenicity of an HIV-1 nef-expressing modified vaccinia virus Ankara (MVA) was investigated in 14 HIV-1-positive patients (CD4 >400/microl) on highly active antiretroviral therapy (HAART). Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well-tolerated except for local reactions, with only mild systemic side effects reported in a few patients. Vaccination with MVA-nef was associated with recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14 patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+ and CD8+ T cells. All patients had been vaccinated against smallpox and a strong T-cell and antibody response to MVA was induced in all patients. After interruption of HAART, viral load rebounded in all patients, but after a median time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART viral load and CD4 counts stayed above the pre-HAART levels. While six patients have remained off therapy for a median time of 64 (57-76) weeks, HAART was resumed in 8/14 patients after a median treatment interruption time of 15 (4-38) weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1-infected subjects and has provided encouraging data on the potential of therapeutic vaccinations.
Harrer
Ellen
E
Department of Medicine III, University Hospital Erlangen, Erlangen, Germany.
Bäuerle
Michael
M
Ferstl
Barbara
B
Chaplin
Paul
P
Petzold
Barbara
B
Mateo
Luis
L
Handley
Amanda
A
Tzatzaris
Maria
M
Vollmar
Jens
J
Bergmann
Silke
S
Rittmaier
Marion
M
Eismann
Kathrin
K
Müller
Sandra
S
Kalden
Joachim R
JR
Spriewald
Bernd
B
Willbold
Dieter
D
Harrer
Thomas
T
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000276:immunology; D004334:Drug Administration Schedule; D000939:Epitopes / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics; D005822:Genetic Vectors; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007167:Immunotherapy; D018655:Lymphocyte Count; D008875:Middle Aged; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D019562:Viral Load; D028761:Withholding Treatment; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral; D015704:CD4 Antigens; D000939:Epitopes; D015693:Gene Products, nef; D014614:Vaccines, Synthetic; D054311:nef Gene Products, Human Immunodeficiency Virus