Since you're adding the envelope protein gene into the PAVE vaccine, is there a chance that vaccine could be both preventative and therapeutic?
It likely would be some antibody effect, but unlikely would be neutralizing antibodies, because the envelope is presented in that conformational form that doesn't reveal very well its component that would induce that neutralizing antibody. So, yes, there would be some antibody response—and hopefully it will add to the benefit. But, it is more likely that it would elicit a T cell response rather than an antibody response.

To your decision to reject this vaccine trial, there must have been some point where, in smaller trials, the PAVE vaccine proved to be safe and at least somewhat effective. It would have had to in order to get to a large trial, right?
No efficacy at all, because it wasn't done in a large enough trial or among at-risk people, who would allow enough infection to occur to see if it would work. All it showed was safety to some degree—I mean, we didn't do a lot patients—but safety in those we looked at. And the fact that it induces an immune response, which one would argue was somewhat better than what you saw in the STEP trial.

There was some argument about that at several meetings. "Somewhat better" is what? A lot better? I didn't think it was a lot better. That gets back to the point I made at the beginning of our conversation: So it elicits a similar immune response [to STEP]. Well, we know that immune response was not associated with protection [from the virus] in the STEP trial, so I'm not even sure that those immunological correlates are the relevant ones. So it really is sort of like we're swimming in the dark because we don't really know what the immunological correlates are. So, that's why I said I don't accept the original proposal for the PAVE trial. It's powered large enough to give you a whole bunch of immunological correlates, which, to me, are irrelevant if the vaccine doesn't work.

First show me a lean, mean trial with as little risk as possible to the people, as few samples as you possibly can to statistically give me a "yes" or "no" as to whether it lowers the viral load. If the answer is yes, then I definitely want to pursue it by getting many more people to see if we can get a good correlate.

So, that brings us to your piece in Science, outlining the way forward for vaccine research...
That was based fundamentally on the summit that we had in March of this year, in which we looked at the basic fundamental role of discovery versus development, animal models, clinical research. We addressed each of those. So, we outline some of the critical issues: Why don't we get a neutralizing antibody response? How will we be able to elicit it? What is a correlate of immunity? What about nonhuman primate models?

Nonhuman primate models can be very valuable, but right now we've got to link them closer to what goes on in the human. For example, the challenges in the nonhuman primate model are homologous challenges, which means you inject them with the same virus that you vaccinate them with. That's not the way it works in the real world. If you vaccinate somebody with a particular strain or a particular component of a virus, it is overwhelmingly likely that they are going to get exposed to something that's a little bit different. So, if you can't protect against a heterologous challenge, we've got to perfect the monkey model a little more, so that we use heterologous challenges.

Also, we need to totally reexamine what we're calling "potential correlates of immunity."

So, there are some basic definitions of success that need to be agreed upon before moving forward?
We need to have answers to some concepts first before we embark on large, empirically based clinical trials. Clinical trials, as we admit in Science, can be an important part of discovery research. You can get discovery doing clinical research. But, we are going to set a much higher bar for going into a very large empiric-type of efficacy trial. We need to have some really good reason to think that there's a reasonable chance that [a vaccine] will work.

5 Comments

1. 1. Mariojosé 04:33 PM 8/1/08

   Amiable readers, to maintain the fidelity we published the article in the original language.
   Las vacunas son una preparación de antígenos que se inyectan en el cuerpo y generan una respuesta de ataque por medio de los anticuerpos que contribuyen a ponerle fin a algún virus o bacteria. Una vez que han sido suministradas en el organismo generan lo que se conoce por memoria inmunológica por lo que, en la mayoría de los casos, vuelven inmune a la persona a esa enfermedad determinada.La inoculación cuenta con antecedentes en China y Turquía, pero la primera vacuna como tal fue inventada, en 1796, por un médico rural inglés llamado Edward Jenner que dio con una forma para combatir la epidemia de la viruela. Jenner, observó que las mujeres que trabajaban ordeñando las vacas contraían una enfermedad que era conocida como la viruela de las vacas, sin embargo, ésta las hacía inmunes a la viruela humana. Así, sacó una muestra de leche de vaca de la mano de una de las granjeras y la inyectó en el brazo de un niño. Éste sufrió los síntomas de la viruela vacuna. Cuarenta y ocho días después, cuando ya no quedaban rastros de la enfermedad, le inyectó una muestra de la viruela humana y éste no padeció ningún síntoma del mal. Basados en esta observación, nosotros planteamos la siguiente hipótesis: las cucarachas son los insectos sobrevivientes más antiguos sobre la faz de la tierra, por su carga atómica que poseen han podido sobrevivir a grandes cataclismos y fenómenos atmosféricos, así también, las terribles bombas atómicas creadas por el hombre.
   Existes miles de variedades de cucarachas, pero específicamente las cucarachas que viven en las alcantarillas y se alimentan de los residuos vaginales, el semen, las heces fecales y los excrementos. Estas han logrado sobrevivir, son inmunes y son portadoras del virus del sida. De igual manera como Edgard Jenner, hizo su investigación se hará es mismo procedimiento. Queremos decir hay que aumentar la capacidad inmune del cuerpo humano, aumentar los anticuerpos para poder resistir y convivir con el VIH/Sida. Cuando el cuerpo recibe esta dosis de virus o bacterias, el sistema inmunológico se pone en alerta y destruye a estos agentes que le son extraños al organismo. Así, cuando una dosis realmente dañina decide atacar, el cuerpo ya se encuentra preparado para reconocerla y atacarla rápidamente. Edward Jenner nació el 17 de mayo de 1749 en Berkeley, condado de Gloucester, Inglaterra y falleció un 26 de enero de 1823 en la propia localidad de Berkeley. Fue un afamado
   investigador, médico y poeta.

   Reply | Report Abuse | Link to this

2. 2. Mariojosé 05:09 PM 8/1/08

   Amiable Readers, the proteins of the cockroach are the solution for the vaccine of AIDS. The director of the NIAID, Dr. Anthony Fausi, must initiate the investigation.

   Reply | Report Abuse | Link to this

3. 3. jpuah23 01:31 PM 12/7/09

   There are many natural ways to rid your body of HIV. In contrast with the traditional antiviral cocktails of medicine today, which cost thousands, have severe side effects, and comes with the double edged sword delema,meaning if the virus doesn’t kill you the cocktails will, this medicine is all natural.Please visit this site for the full information about this subject……http://pushgood-nomorehiv.blogspot.com/

   Reply | Report Abuse | Link to this

4. 4. dlanasa 09:54 AM 9/20/10

   I read a testimoney that coconut milk can stop AIDS; monolaurine can be purchased as the nutrient found in the coconut milk.
   There was a doctor from India that said he stopped the AIDS virus with a mixture of spices. I read the abstract about 7 years ago; it is on medline. I vaguely remember he called the mixture with a word that begins with "K". And what about Safi sold in East Indian grocery stores. There are so many foods that support the immune system, why do they not talk too much about them?

   Reply | Report Abuse | Link to this

5. 5. dlanasa 09:57 AM 9/20/10

   I read a testimoney that someone was healed of AIDS with coconut milk; monlaurine is a nutrient from that food that can be purchased from the health food stores.
   Also, I read an abstract of a study that a doctor from India stopped the sickness with some spice mixture that began with a "K" about 7 reads ago I read it. What about Safi? Can be purchased in an East Indian grocery store. So many foods support the immune system. Why is not diet mentioned more?

   Reply | Report Abuse | Link to this