[lbeltrame]

Compared to the other vaccines in study, this one has a significant limitation: a lot of the population has antibodies against the Ad5 vector used to deliver the antigen, which significantly lowers the efficacy. High doses to contrast this effect were met with adverse events, so this means that Phase 2 and 3 protocols will need to be adjusted.

[toufka]

Would the use of the Adenovirus vector used here foreclose future gene therapies delivered with a similar vector? If so, that could devastate in one go a lot of people’s ability to get specific therapies as they start to come online in the next decade.

[lbeltrame]

It is actually a very known problem for gene therapies. IIRC, similar vectors were used in the past, with the same problem, of course.

[nknealk]

Here’s the critical paragraph from results. I think another path forward would be to keep the low/medium dosing but titer for lack of Ad5 antibodies before qualifying a patient for the vaccine.

> Before vaccination, 20 (56%) participants in the low dose group, 19 (53%) participants in the middle dose group, and 16 (44%) participants in the high dose group had a high pre-existing Ad5 neutralising antibody titre (>1:200). Only five (25%) participants of 20 in the low dose group, seven (37%) participants of 19 in the middle dose group, and ten (63%) participants of 16 in the high dose group, who had high pre-existing Ad5 immunity, had at least a four-fold increase in neutralising antibody titre at day 28 post-vaccination (appendix pp 8–10). Multivariable analysis showed that high pre-existing Ad5 neutralising antibody titres compromised the seroconversion of neutralising antibody post-vaccination, regardless of the vaccine doses, and recipients aged 45–60 years seemed to have lower seroconversion of neutralising antibody compared with the younger recipients (appendix p 11). The Ad5 neutralising antibodies were significantly boosted post-vaccination (appendix p 12).