vaccine candidate Hill did think was promising was a vaccine or vaccine concept
called HIV Conserv, currently being taken forward by Professor Andrew
MacMichael’s team at Oxford University in a series of trials called HIVCORE.
This had generated an immune response as high as 5000 SFUs – ten times as
potent as HVTN 505. Unsurprisingly, HIV Conserv was the second-most talked about
vaccine of the conference, after Louis Picker’s CMV-based vaccine (see
Hanke of Oxford University explained the concept behind HIV Conserv.
vaccines incorporating actual genes or gene sections from HIV generate
‘wasteful’ immune responses, in that the most immunogenic parts of HIV are also
the most genetically variable ones. This means firstly that it is very
difficult to create a vaccine that works with a large variety of different
viral subtypes and secondly that the immune response is one that the virus can
easily escape (mutate itself away from).
Conserv is a ‘chimeric’ vaccine, meaning that, like a Frankenstein’s monster,
it is stitched together from different parts of HIV that do not lie next to
each other in nature. It is made up of a chain of 14 different pieces of the
HIV genome, the majority from the polymerase (pol) gene, that combine
immunogenicity with the property of being highly ‘conserved’. This means that
they vary little between viral subtypes, because HIV finds it difficult to
mutate away from them without becoming a very much less ‘fit’ and
poorly-replicating virus in the process.
first HIVCORE trial packaged the HIV Conserv gene-string in three ways – as a
plasmid (a naked ring of DNA), and inside two viral vectors, an MVA virus (like
ALVAC) and an adenovirus (as in STEP,
Phambili and HVTN 505, except that this vector came from a chimp rather than a
human adenovirus, for added safety).
researchers gave volunteers the HIV Conserv vaccine in three different
regimens: as chimp adenovirus then MVA (CM): as three shorts of DNA then chimp adenovirus then MVA (DDDCM): or at the
same regimen but with MVA before the adenovirus (DDDMC).
vaccines were highly immunogenic, generating CD8 cell responses to HIV of 5150
SFUs for the CM regimen and 5800 for the DDDCM regimen (the third regimen CD8
response was 2000 SFUs, which is still good but not as good as the others).
Furthermore, the immune response seems quite persistent, with responses of 600
and 1500 SFUs after a year for the DDDMC and DDDCM regimens respectively.
does not always mean efficacy; so the researchers also took immune-stimulated
CD8 cells out of volunteers’ bodies and incubated them with CD4 cells and HIV
of three different subtypes: the virus was stopped from infecting the CD4 cells
in 15 out of 23 cases.
HIVCORE trials will now move forward into trying further experimental regimens from
the Conserv vaccine, in Oxford, London and Nairobi. Since complete protection
from HIV will need an antibody response as well as a CD8 response, MacMichael’s
team are working with IAVI to develop an antibody-stimulating vaccine to go
alongside the Conserv vaccine.
a CD8 vaccine, HIV Conserv could also work as a therapeutic vaccine in people
with HIV, possibly as part of a cure or HIV-remission study. It could help to
supress the last remnants of HIV in cells after the majority of the
HIV-infected cells had been purged by immune-stimulating drugs and
antiretroviral therapy (see this
team based in Barcelona will be looking at the use of the CM Conserv regimen in
people who started HIV therapy in the first six months after infection, to see
if they might be able to stay virally undetectable when their ART is
discontinued. So far 24 people have received the chimp adenovirus and, of
these, eight have received the MVA virus too.
will have data on the immunogenicity of this regimen by summer 2014. This and
similar research, including the CMV vaccine too, hold out the promise that a
cure for HIV and something that prevents it may look very similar; certainly, cure
and vaccine research are starting to move together into a useful synergy.