
Mosaic HIV Vaccines in Late-Stage Trials - apsec112
https://www.verywellhealth.com/mosaic-hiv-vaccine-sparks-hope-4173079
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apendleton
I was thinking it'd be a huge bummer to this team if one of the Ad26 Covid
vaccines ends up the frontrunner, and it ends up that tons of people have
preexisting immunity to Ad26 when it comes time to give them this new HIV
vaccine, but it turns out Janssen (who's behind the leading candidate here)
_also_ has an Ad26 Covid trial, so I guess they're not that worried about it?
If not, I wonder why not... some of the other adenovirus Covid trials, at
least, suggest poorer performance in Phase 1 trials in people with preexisting
immunity to either the actual adenovirus strain or the vaccine, so my
impression was that for any given adenovirus strain, you pretty much only got
one shot at using it to vaccinate (no pun intended).

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schoen
Interesting! Could they deliberately mutate the strain in ways that decrease
people's pre-existing immunity to it, before engineering it to become an agent
to deliver the vaccines?

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apendleton
I don't think so, or at least, the Covid vaccine trials so far suggest that if
it is possible, they either haven't done it or it didn't work, given that some
study participants _did_ have pre-existing exposure, and it made the vaccine
work less well. Worse still: older people, having had more opportunities for
exposure over their lifetimes, were most likely to experience this outcome.
Slight caveat, I guess, that where I've seen this discussed, it's been about
CanSino's Ad5-vectored vaccine, rather than any of the Ad26 ones, but I don't
know of any reason it'd be different.

From what I understand, part of the reason that the Oxford group chose a chimp
adenovirus was specifically to avoid this issue, as the odds of people having
been naturally exposed to chimp adenoviruses is probably pretty low.

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vertis
From my very very limited understanding isn't the adenovirus just a delivery
mechanism? Is there a dependency on ad26 that would mean nothing else could be
the delivery mechanism?

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epmaybe
I'd imagine that ad26 is just the serotype used, and so if you used a
different serotype for other vaccines that don't have much cross
immunogenicity, you'd be in the clear.

