Background: To be effective against HIV-1, vaccine-induced
T cells must selectively target functionally conserved and, at
the same time, protective epitopes present on the majority of
currently circulating and reactivated HIV-1 strains, and rapidly
reach protective frequencies upon exposure to the virus.
Heterologous prime-boost regimens using virally vectored
vaccines are currently the most promising strategy towards
achieving this goal, nevertheless, induction of robust longterm
memory remains challenging. To this end, lentiviral
vectors induce high frequencies of memory cells due to their
low-inflammatory nature, while typically inducing only low antivector
immune responses.
Methods: We describe construction of novel candidate vaccines
ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an
integration-deficient lentiviral vector platform with preferential
transduction of human dendritic cells and express bivalent
mosaic of conserved-region T-cell immunogens with a high
global HIV-1 match.
Results: Each of the two mosaics was individually immunogenic
and together in heterologous prime-boost regimens with nonreplicating
simian (chimpanzee) adenovirus or non-replicating
poxvirus MVA vaccines induced very high frequencies of
plurifunctional and broadly cross-reactive T cells in BALB/c and
outbred CD1-SWISS mice.
Conclusions: These data support further development of this
vaccine concept