report in Nature journal3
about the CMV-based vaccine was picked up by the mainstream press
and, as with many recent scientific advances in the HIV field, was hailed as if
it was the next step to a cure.
What happened in this trial is that, in three separate batches, 46 rhesus monkeys
were given the RhCMV/SIV vaccine. Then, 13 months later, they were exposed to
SIV: 24 male and female monkeys with up to ten weekly shots of virus in the
rectum to mimic anal sex, 16 females similarly infected vaginally, and six with
up to three direct low-dose injections of SIV to mimic needle sharing. They all
acquired SIV, as blood and cellular assays taken soon after infection show.
The bad news,
and the reason this is not ‘the cure’, is that for 22 (48%) of the monkeys, the
vaccine did not work. (By October, 96 had been infected and the vaccine did not
work in 48 of them.) They developed SIV infections with high viral loads,
including four of the six monkeys infected via injection. That also means they
would die within a year or two unless treated with antiretrovirals: the SIV
strain chosen is highly pathogenic and typically maintains long-term blood
viral loads of a million copies/ml or more. Another reason that this is not
‘the cure’ is that this is an animal study and, so far, promising signs of
success in animal studies have often failed to translate into anything more.
reason for more cautious reporting, is that some researchers are concerned that
CMV is not safe enough to use in a vaccine for humans; the very fact that it is
so active and stimulates such a strong immune response worries people that,
through recombination (the so-called ‘viral sex’ where these little entities
swap genes), HIV could reconstruct itself from the vaccine.
The good news
is this: the other half of the vaccinated monkeys also became infected with
SIV. There was no doubt that SIV was there: as we said above, it showed up in
cells. But it was such a pathetic, low-key infection that these monkeys never
even made antibodies to the virus – meaning they would test SIV negative. The
blood viral load in most of these 24 monkeys was never above five copies/ml,
though five showed irregular blips up to 10,000 copies/ml in the first three
months after infection but never after (with one crucial exception, which we’ll
hear more about below).
vaccinated monkeys were put down five weeks after being vaccinated so they
could be autopsied. They had traces of SIV in 2% of samples of immune tissue
(from lymph nodes, spleen, gut, bone marrow and liver). That compares with 100%
of samples in an infected but unvaccinated monkey; 16% of samples in a monkey
that spontaneously controlled its viral load; and 6% of samples in a monkey on
antiretroviral drugs (tenofovir, raltegravir and boosted darunavir).
the viral protein vif from the
vaccine, the researchers were able to show that it was immune responses
generated by the vaccine, and not ones generated by the virus, that were
controlling the infection.
strong immune responses to the other proteins were already present at the date
of infection – an immune response to vif
did not reach similar levels till two weeks after infection.
thing about this vaccine, however, is that even this low-level infection
disappeared over time. When aidsmap.com first reported on this study two years ago,
any trace of viral infection had disappeared in 72% of the monkeys infected
rectally a year after infection. Now, three years after infection in the
rectally infected monkeys and after at least a year in the monkeys infected
vaginally and via injection, blood tests and cell samples could find no trace
of virus in any of the monkeys that
had an undetectable blood viral load. Furthermore, while levels of immune
response to the vaccine remained strong, levels of immunity to SIV itself had
dwindled to nothing by a year after infection, because by that time there was
so little virus around the immune system couldn’t sense it.
stringent tests were done on some monkeys. Even more ultrasensitive assays on
six autopsied monkeys found no trace of virus. Three had their CD8 cells
depleted by immunosuppressant drugs: no virus reappeared. And finally, in an
experiment you could never do in humans, immune cells were transplanted from
seven vaccinated monkeys, two monkeys on ART, and the one ‘elite controller’
monkey, into ten uninfected monkeys. None of the seven monkeys receiving cells
from vaccinated monkeys developed SIV infection; the other three all did.