Dora ha scritto:Riporto in questo thread una notizia che Cesar ha segnalato oggi
altrove, perché si collega a un discorso che stavamo facendo qui:
Ho notato una cosa: il vaccino appena fallito -
trial HVTN 505 - usava il medesimo vettore Ad5 (adenovirus 5) che si ritiene responsabile del fallimento del vaccino della Merck.
Vorrà dire qualcosa che anche in questo caso si sono infettate più persone che avevano fatto il vaccino rispetto ai controlli che non l'avevano fatto (non si è raggiunta la significatività statistica, ma è un dato inquietante, da non sottovalutare)?
Non sarà un segnale che quell'adenovirus 5 è meglio non usarlo?
È di pochi minuti fa la pessima notizia del fallimento in fase clinica di un altro vaccino basato sull'adenovirus 5, un candidato vaccino chiamato DNA/rAd5.
Il trial (con placebo e su 2504 uomini o transgender che hanno sesso con uomini) è stato interrotto, perché i risultati parziali dimostravano che chi aveva ricevuto il vaccino si infettava quanto chi aveva ricevuto il placebo (27 infezioni in chi aveva ricevuto il vaccino, 25 in chi aveva ricevuto il placebo su 1914 partecipanti già vaccinati). Per di più, si è visto che il vaccino non aveva nessuna influenza nell'abbassare il set point virale (HIV RNA 4,46 log copie/ml vaccinati; 4,47 placebo). (**)
Basta con l'Ad5 o vogliamo far infettare ancora altre persone?
P.S. Gus Cairns - tutto bello giulivo - ha appena pubblicato su aidsmap un post dal titolo e dal tono in controtendenza rispetto all'umor nero di questo mio messaggio: HIV vaccine conference opens in most promising research atmosphere for years. Non so se non aveva ancora ascoltato la presentazione di Hammer o se si aspettava il fallimento del DNA/rAd5 e l'aveva già metabolizzato ... 
HIV Vaccine Candidate Bites the Dust
Published: Oct 7, 2013
By Michael Smith, North American Correspondent, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania
Another HIV vaccine candidate has failed to protect against the virus, leaving AIDS researchers disappointed but not discouraged.
A placebo-controlled clinical trial of the latest vaccine was halted by its data safety monitoring board because interim results gave little hope that the drug would work, according to
Scott Hammer, MD, of Columbia University in New York City.
The number of infections was similar whether participants got the vaccine or placebo, Hammer reported online in the New England Journal of Medicine and at the AIDS Vaccine 2013 conference in Barcelona.
The vaccine also had no effect on the so-called viral set point, the level at which the virus settles in the blood after infection and before antiretroviral treatment. The set point is a marker for the aggressiveness of the infection -- a higher setpoint leads to a faster progression to AIDS in the absence of treatment.
The study "gave a definitive, albeit disappointing, result," Hammer and colleagues reported.
On the other hand, "we've learned a tremendous amount" from each trial of an HIV vaccine candidate, commented Col. Jerome Kim, MD, acting director for the U.S. Military HIV Research Program in Silver Spring, Md.
And despite the "multiple disappointments," Kim told
MedPage Today, the many trials have really only tested four separate vaccine concepts and each has increased scientific understanding of how HIV and the host immune system interact.
Of the proposed HIV vaccines to date, only one -- a prime-boost combination tested in Thailand by a research group that Kim was part of -- has had any benefit and that was a modest 31% protective effect.
Two early trials, in injection drug users and men who have sex with men, used HIV proteins in an attempt to elicit immunity, but without effect.
At least one vaccine candidate -- the
MrkAd5 drug tested in the so-called STEP trial -- actually increased the risk of acquiring HIV.
"We're learning a lot along the way,"
Michael Saag, MD, of the University of Alabama Birmingham, agreed.
"If we didn't try," he told
MedPage Today, "we wouldn't have a chance."
But it's a "tall order," Saag said, to create a vaccine that will do what the human immune system generally cannot -- prevent or clear HIV infection.
"What this study is telling us is that this virus is tough," he said.
The current failed vaccine candidate is a combination of sections of HIV-derived DNA intended to prime the immune system, followed by an adenovirus vector expressing HIV proteins to boost the immune response.
The primary endpoint was HIV infection during the period after the complete series of injections through the end of 24 months of follow-up -- the rate of what the investigators called 28+ infection.
The trial enrolled 2,504 men or transgendered women who have sex with men who were regarded as being at high risk for HIV.
When the safety committee pulled the plug, Hammer reported, 1,914 participants were available for analysis and there had been 27 infections in the vaccine group compared with 21 in the placebo group.
The difference was not significant, but yielded a vaccine efficacy of negative 25%, the researchers found.
The secondary endpoint of viral setpoint -- measured among those who acquired the virus -- also showed no difference: average plasma HIV RNA loads of 4.46 and 4.47log10 copies per milliliter in the vaccine and placebo recipients, respectively.
The vaccine elicited both cellular and humoral immune responses, Hammer and colleagues found, but they had no effect on infection risk.
On the plus side, the vaccine was safe, the investigators found.
"I'm really happy that it didn't cause harm," commented Carlos del Rio, MD, of Emory University in Atlanta, who was one of the investigators of the STEP trial.
"I was really skeptical that it was going to work," Del Rio told MedPage Today. "My biggest concern was that it was gong to be harmful."
His concern was centered on the recombinant adenovirus-5 vector, which in the STEP trial appeared to be associated with the increased risk of HIV among those who got the vaccine candidate.
"The study should never have gone forward," he said. "The scientific rationale to do it, after STEP, was in my mind not there." (*)
The study investigators pointed out that the vector they used was not the same one used in the STEP trial -- more of the adenovirus genome was deleted and it included the HIV env gene.
The study was originally intended to include 1,350 participants and to look just at viral load setpoints, but was eventually expanded to allow study of prevention efficacy and to account for possible effects of pre-exposure prophylaxis.
"There's such an urgency to find an effective vaccine," Del Rio said, that investigators might have jumped the gun.
"The bottom line is that we need a vaccine, but the road has been full of disappointments," he said.
Saag and Kim both noted that not all of the HIV vaccine eggs are in one basket. A great deal of research, Saag said, is "churning in the background."
Among other things, Kim said, researchers are investigating the use of other adenoviral vectors and different combinations of HIV proteins and genes. Basic research is also focusing on concerved regions of the highly variable HIV genome and on finding broadly neutralizing antibodies.
The study had support from the National Institute of Allergy and Infectious Diseases, Columbia University's Clinical and Translational Science Award from the National Center for Advancing Translational Sciences, the NIH Intramural Research Program, the Emory Center for AIDS Research, the Harvard Center for AIDS Research, the Baylor–University of Texas Houston Center for AIDS Research, the Colorado Clinical Translational Science Institute, and the National Center for Advancing Translational Science.
Hammer said he had no relevant conflicts.
(*) DdD: come fa Del Rio a dire che "almeno il vaccino non ha fatto del male"? Ai volontari che si sono infettati non ha fatto del male? Si sapeva che il vaccino della Merck era stato un disastro proprio per l'Ad5 (e anche tutti gli studi che sono stati fatti dal 2007 a oggi - e che continuano - lo confermano); si sapeva che era fallito il trial del NIAID della primavera scorsa proprio per l'Ad5; e ci viene a dire "almeno non ha fatto del male"?! 
Articolo:
Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
******************************
(**) Errata corrige - 8 ottobre 2013.
Ho letto l'articolo di Scott Hammer sul NEJM, perché c'erano troppe cose che non mi tornavano nell'articolo di Michael Smith su MedPage Today (primi fra tutti i "numeri" dei contagi e dei set point, che mi parevano vecchie conoscenze) e devo rettificare il post che ho scritto ieri: il trial di cui si parla è lo stesso che è stato sospeso la primavera scorsa, cioè l'HVTN 505. Quindi non si tratta di due candidati vaccini falliti che usavano l'Ad5, ma di uno solo.
Gus Cairns ha avuto dunque tutto il tempo per metabolizzare la delusione.
Mi scuso per aver dato per buono che Michael Smith sapesse di che cosa stava parlando e per la confusione che posso aver generato.
La lezione ad AIDS Vaccine 2013 in cui Magdalena Sobieszczyk cerca di capire le ragioni del fallimento del trial HVTN 505 può essere vista qui: http://www.aidsvaxwebcasts.org/console/ ... Type=audio&.