Safety and immunogenicity of ChAd.HIVconsv and MVA.HIVconsv therapeutic vaccines in a cohort of early treated HIV-1 infected individuals
Background: T-cell
vaccines targeting the most conserved regions of the HIV-1 proteome may be
required for the elimination of the latent viral reservoir. HIVconsv
vaccines vectored by chimpanzee adenovirus (ChAdV63) and modified vaccinia
virus Ankara (MVA) have shown to
induce high levels of effector T cells in healthy individuals (HIVCORE02 trial).
BCN01 (NCT01712425) is a phase I study to evaluate the safety and immunogenicity of
ChAdV63 and MVA.HIV-consv vaccines in early-treated HIV-1 infected individuals
Methods: 24 individuals identified with
recent HIV infection (< 6m from acquisition) who initiated
Tenofovir/Emtricitabine/Raltegravir within 1 week after diagnosis, received an intramuscular
ChAdV63.HIVconsv (5x1010vp) vaccination after 6 months under
cART. Participants were given an
MVA.HIVconsv booster immunization (2x108pfu) 24 or 8 weeks afterwards
and were followed for 6 months. Local and systemic events were recorded for a
minimum of 7 days following each immunization. Immunogenicity to
the vaccine insert and the rest of the HIV-1 proteome was assessed by IFNg
ELISPOT.
Results: Local and systemic events after vaccination
occurred in 22/24 individuals, mostly severity grade 1-2 and transiently (48
hours). Local pain was more often reported with MVA than ChAdV63 vaccination. Responses to conserved
regions before cART initiation were only observed in 4 individuals and
diminished significantly after achieving viral supression. All participants significantly increased T-cell responses
that targeted the vaccine insert, with a peak 1-4 weeks after MVA vaccination (median
of 1,015 SFC/106 PBMC,
range 140-6,805, p=0.0003, Wilcoxon t-test compared to baseline). Over
vaccination period, no unspecific expansion of T cells targeting HIV-1 regions
outside HIVconsv insert or CEF was noted, allowing for an optimal focusing of T-cell
responses on conserved regions (48% of total HIV immune response being
HIVconsv-specific 4 weeks after MVA vaccination). Among vaccinees, no significant differences in
peak immunogenicity was observed between
short and long prime/boost regimen.
Conclusions: ChAd.HIVconsv and MVA.HIVconsv was a safe strategy to shift pre-existing immune response towards
conserved, vaccine-encoded regions of HIV in a cohort of early-treated individuals
and may set the stage for successful subsequent of cure strategies.
B. Mothe1,2,3, C. Manzardo4, P. Coll1,2, P. Cobarsi2, A. Sanchez-Bernabeu1, R. Escrig2, N. Perez-Alvarez2,5, J.M. Miró4, L. Dorrell6, B. Clotet1,2,3, T. Hanke7, C. Brander1,3,8, BCN01 Study Group
1IrsiCaixa AIDS Research Institute - HIVACAT, Badalona, Spain, 2Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain, 3UVic-UCC, Vic, Spain, 4Hospital Clínic-IDIBAPS, Barcelona, Spain, 5Technical University of Catalonia, Barcelona, Spain, 6John Radcliffe Hospital, Oxford, United Kingdom, 7The Jenner Institute, Oxford, United Kingdom, 8ICREA, Barcelona, Spain