The Scripps researchers’ study was designed as a proof of
concept study rather than an efficacy or dose-finding study. Its aim was to show that
protective levels of broadly neutralising antibodies could be achieved with a
single HIV vaccine inoculation, and to find out what level of antibody response
would confer protection against HIV.
The researchers vaccinated 78 monkeys. Because of their aims, they then picked the monkeys with the six highest antibody
responses and then matched them with six of the low-responders, matched for gender,
age and weight. They also compared these responses with six control monkeys who
were not vaccinated but were challenged with a monkey-adapted form of HIV
(simian HIV, or SHIV) – as were the vaccinated animals.
The viral challenge consisted of six weekly rectal doses of
the pathogenic SHIV BG505 virus, which was the one whose envelope protein was
used as the basis for the vaccine. Again, because this is a proof-of-concept
study, the researchers wanted vaccine and virus to be the best ‘fit’ possible.
In later studies, one would want to use other viruses to demonstrate that the
antibodies generated by the vaccine had the broadest efficacy possible. The virus
dose given should, it was calculated, infect at least 75% of monkeys after one challenge.
The SHIV BG505 challenge was introduced four weeks after the
vaccine inoculation. In the high-titre monkeys, because only two out of six
were infected after six challenges, the researchers waited for five weeks and
then gave six more weekly challenges.
Antibody response is measured by titre. This means the
degree to which blood plasma or other antibody-containing fluid has to be
diluted before the antibodies become undetectable in an assay. This is an
easier and more reliable test than directly quantifying the amount of antibody
The six highest responders had an average antibody titre of
1:3750, meaning that antibodies in their blood plasma remained detectable up to
a solution of one part blood plasma in 3750 parts of saline. The average titre
of the lower responders was 1:103, or a 36-fold lower response.
Interestingly this was a lot higher than the antibody
response seen in control animals when they were infected, which ranged from
1:102 in the highest responders to less than 1:10 in the lowest responders.