This year AIDS vaccine conference held in Barcelona highlighted some new and interesting developments but also showed that as an event it was starting to run on empty.
A tale of two trials (one in Monkeys, one in Humans)
The tag line “Progress, Partnership and Perseverance” said it all. No climax, no new directions or U-turns, but a call for a continued and concerted effort in the search for an elusive HIV vaccine with a renewed interest for replicative vaccines.
The approach spearheaded by Louis Picker is not new but recently drew considerable attention after an article in Nature reported a 50% protection in a Non-Human Primates study (for a lay summary read Gus Cairns article at Aidsmap). Live, persistent vaccines remain present and active for the life of the vaccinee and allow for a continuous stimulation of the immune system, preventing the waning of the immune response observed in animal and human studies (including the RV144 Thai trial that showed a more promising protection effect after a year than by the end of the study, though not statistically significant). Though attractive, replicative vaccines are not without substantial risk of pathogenesis in pregnant women and immunocompromised individuals (Herpes viruses were also suggested as an alternative).
The conference was also an opportunity to officialise the death of Adenovirus 5 vectors. A meta-analysis of the Merck-Ad5 Phambili and STEP trials and VRC-Ad5 HVTN 505 trials presented by Peter Gilbert confirmed that altogether Ad5-based vaccines enhanced the risk of HIV acquisition by 33%; however this enhancement was driven by the Merck Adeno 5 vector and was not observed in the HVTN 505 study which used a different vector and was tested in a different population, making the comparison somewhat difficult. Nonetheless, the outcome of this analysis is that a number of studies (even those using Chimpanzee Adenovirus) have been put on hold and are under review with investigators starting to look for alternative vectors.
Trials and errors often mistaken for Design
Antigen design and the evolution of the immune response towards broadly neutralising antibody were discussed in several talks (watch the excellent Penny Moore for more on the former), but though these are fascinating, how they can be translated into the real world remains a thorny issue, if only because of manufacturing challenges but also cost and feasibility of immunisation regimens requiring multiple injections of similar but different products over long periods of time.
The work presented often revolved around a “Mr Wok” approach: Chose you vector, chose your insert, chose your animal model and your regimen and then run your favourite assays, ELISPOT being mandatory even if many wonder what this assay means and how relevant or predictive it is of what will happen when products will be tested in humans. The lack of harmonisation between labs, or of agreement on what assays should be done and why, led researchers to entrenched positions about what to do, somewhat slowing down the field.
This could not be better encapsulated by Prof Adrian Hill, Oxford malaria vaccine expert, who said, “We should all get out a bit more, see a bit more, hear about other stuff, we should focus on vaccine candidates with a plausible immunological basis (sounds totally obvious doesn’t it), accelerate and run more informative clinical trials and recall that chance events happen by chance much more often than you’d think”, adding that, “RV144 might have been some efficacy but it’s not very convincing it may be chance”.
Relighting the fire
The conference is somewhat losing momentum after the excitement of 2009 and RV144. It is still a great place to meet colleagues and learn about what they are doing but my feeling is that is it time to move on, be bold and get to meet people from other prevention fields such as microbicides, but also ARV, be it for treatment of for prevention and of course to instil a good dose of social sciences into the meeting. This is why next year conference (tediously) called “HIV Research For Prevention” or HIVR4P is offering the promises of interesting synergies, should all players be willing to get into the spirit of the event.
For instance the need to integrate the results arising from trials of different biomedical interventions was only mentioned in passing in one session by Scott Hammer who stressed the need for HIV vaccines studies to take into account the results of PrEP studies and consider integrating both approaches in one trial; though controversial for a number of reasons (to be explored in a forthcoming post) the possibility and feasibility of such approach had been discussed a year earlier in more details during the Microbicides 2012 conference in Sidney.
The continuing recognition that a vaccine is key to end the epidemic but that it will not be enough on its own explains and justifies the need to bring together a number of events, researchers, clinicians, advocates and journalists under the same roof.
Already this year a number of satellites and sessions not strictly about basic science, signalling a departure from a programme usually dry for attendees not familiar with basic research. These provided an opportunity for all to mingle in a friendly atmosphere. The “Speaking Science to the Public” organised by AVAC allowed for researchers and journalists to share their experience of miscommunication and raised the challenge of defining in less than a minute basic vocabulary (as basic as “antigen”) and also more complex concepts (such as VISP).
As the fields of HIV, its biology, its transmission, treatment and prevention are becoming more integrated, it is becoming more and more important for scientists to learn how to engage and speak with journalists, for journalists to learn the basics of HIV research and for advocates to take the opportunity to act as a reliable link between the researchers and the public.
A widening strongly grounded in hard science
The conference ended with Jose Esparza giving a comprehensive history of the search for an HIV vaccine and delivering the message that more than ever we needed to pursue the search for an HIV vaccine. Robin Shattock and Eric Hunter, two of the five chairs of next year HIVR4P 2014 conference to take place in Cape Town, introduced it as an event firmly anchored in and driven by scientific research and as the only biomedical HIV prevention conference that will take place in the future. This raised some concerns about how much social sciences there will be and about the balance between different biomedical interventions in a field where HIV vaccine research gets the lion’s share of funding (USD$847m in 2012 compared to USD$245m for microbicides and USD$31m for PrEP according to an AVAC report). But having discussed this with one of the chair, it is clear that the message was aiming at reassuring an audience that fears the event could turn into another IAS conference.
The HIVR4P will remain a small event expecting about 1,500 attendees, scholarships will be provided to insure that advocates and representatives from developing countries can attend the event (unlike the “What will it take to achieve an AIDS-Free World” conference organised by The Lancet and Cell). A number of cross-topic sessions are already planned.
The event will be a test of how well various fields can come together at a time when the number of new HIV infection remains stable worldwide year on year, when the human rights of those most at risk are still challenged and curtailed and where the global or even national economic crisis are still threatening progress towards and AIDS-free generation, whichever generation that may be.
On this note, I look forward to next year event in Cape Town.