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FAQS
1. What is a vaccine?
A vaccine is a product which stimulates the immune system to combat a particular pathogen (a disease-causing
microorganism, such as a virus, bacterium, or parasite). Nowadays, several types of vaccines exist. Vaccines can
be a live attenuated form of the pathogen (a version of the microbe that has been changed to reduce or eliminate
its potential to cause disease), an inactivated or "killed" pathogen (which contain microbes that have been
inactivated with chemical, heat or radiation) and subunit (which contain just the antigens of the microbe that best
stimulate the immune system).
Usually, vaccination programs have positive effects on the whole population, because the vaccination of a critical
number of people in the community reduces the incidence of the infection ("herd immunity" effect).
2. What is the meaning of "immunity" and "immune response"?
Immunity refers to a state of the host to avoid infection or disease, which depends on the effectiveness of the
immune response against a particular pathogen. Vaccines are aimed at inducing protective immune responses
against that pathogen, thus conferring immunity to the host.
3. Do vaccines have any side effects?
Modern vaccines are highly safe, well tolerated and immunogenic. The advantages of being vaccinated are more
than the side effects, which are usually limited to fever, soreness or redness at the injection site.
4. What is a preventive vaccine?
A preventive vaccine aims at preventing an infection or a disease in an uninfected individual.
5. What is a therapeutic vaccine?
A therapeutic vaccine aims to either induce or boost a specific immune response to a virus/bacterium in
individuals already infected, to reduce the impact of a disease / infection.
6. What is a clinical trial?
A clinical trial is an evaluation study aimed at assessing whether a certain treatment (drug or vaccine) is suitable
for human use, in terms of both safety and efficacy. During a clinical trial, the product to be evaluated is
administered under tight medical supervision, in order to assess whether it might be noxious, whether it might
cause any side effects, whether and to what extent it is efficacious against the disease it is indicated for, and to
determine the best dose and treatment regimen. Clinical evaluation of a new vaccine or drug product consists of 3
subsequent phases, called phase I, II, and III.
The clinical phase of experimentation is always preceded by preclinical studies, through which the treatment is
evaluated in laboratory (including animal model testing) in terms of chemical, physical, and pharmacological
profiles, before deciding whether or not to proceed to testing in humans.
7. What is a Phase I trial?
A phase I clinical trial consists in the experimental administration of a drug to humans. It is conducted on a very
small number of volunteers. Patients can be healthy or affected by the disease which the vaccine aims to prevent
or cure. The major goal of a phase I study is to evaluate vaccine tolerability and safety on humans.
8. What is a Phase II trial?
Once Phase I trial has shown the experimental drug is safe and well tolerated, it can move to Phase II. The
number of participants is usually low, even though higher than in Phase I. The major aim of Phase II trial is to
assess the efficacy of the drug at inducing a specific immune response. Nonetheless, safety and tolerability
evaluation is not disregarded. The results of this Phase are aimed to demonstrate the drug immunogenicity and to
define doses and administration protocols. Phase II trials can be conducted either to define new indications and
doses for commercialized drugs, or to test treatment combinations aimed at reaching a synergistic effect that can
improve treatment efficacy. This phase usually lasts at least 2 years.
9. What is a Phase III trial?
Once Phase I and II trials have given positive results, the study can move to Phase III. In this phase, the drug is
administered to a higher number of patients (thousands), in the doses and means that have been previously
defined. Given the higher number of volunteers, the researchers can collect more information than those received
in the previous phases, especially concerning adverse events and rare diseases. This phase is aimed at proving
both preventive and therapeutic advantages of the drug. A Phase III trial can last about 2-4 years and, in case of
positive results, the treatment can be registered and widely distributed.
10. What is an Observational Study?
Observational Studies are trials in which no experimental treatment is administered. They are aimed at evaluating
a specific characteristic of a sample of subjects in order to assess its real value (descriptive studies). Other
studies are aimed at assessing the relationship between two variables within a sample of subjects (analytical
studies). Therefore, differently from clinical trials, the events observed during an observational study are only
recorded and described, without any clinical intervention by the investigator.
11. Design of a clinical trial
In a clinical trial volunteers can be divided either in a unique group (using the experimental treatment) or randomly
assigned (randomized) to several groups with the aim of comparing treatment efficacy and safety with a
commercialized product or a placebo (pharmacologically inactive product). To this aim, a clinical trial can be: 1)
Open Label: both the experimenter and the volunteer are aware of what has been administered; 2) Single-Blind:
one of the parties is not aware of what product is being administered; 3) Double-Blind: neither the experimenter
nor the volunteer are aware of what product is being administered.
12. What is the informed consent?
By the informed consent a volunteer confirms his/her availability to participate in the trial after having been clearly
informed about all the major issues: (aim of the study, potential risks and advantages, rights, length, etc.) in order
to decide the study participation in an autonomous, responsible and conscious manner. The legal procedure to
release the informed consent consists of filling in, dating and signing a form, both by the patient and the doctor.
To release an informed consent does not limit in any way the rights of the volunteer, since he/she can exit the trial
at any time without an explanation.
13. What kind of vaccine is the Tat-based one?
It is a vaccine against HIV/AIDS which is based on the HIV-1 Tat protein, which is crucial to the virus replication
(Tat protein promotes virus replication in infected individuals and for this reason it is called "regulatory protein"),
its transmission from cell to cell, and for the progression of the disease. It is more conserved in its immunogenic
domains than the envelope proteins (called "structural proteins") used in the most HIV vaccine candidates tested
so far. This means that the parts of the protein that are recognized by the immune system do not change much
over the course of infection, and are therefore very similar in different patients, including those from other
continents, such as Africa, who are infected with viral strains very different from those present in developed
countries.
14. Will the Tat vaccine protect me from infection with HIV?
This vaccine is still under evaluation, thus we cannot foresee whether it prevents the infection or control virus
replication, blocking progression to AIDS.
15. Is the Tat vaccine both preventive and therapeutic?
This vaccine could reduce viral replication and, thus, it can be used both as a preventive vaccine that blocks the
initial cycles of virus replication, preventing HIV spread in the organism, and as a therapeutic one, because the
reduction of viral replication, similarly to anti-retroviral treatments, can slow or block disease progression in HIV
positive individuals. To verify whether this vaccine is an acceptable and efficient treatment against HIV infection
may take many years.
16. Is the Tat vaccine 100% effective in preventing disease?
Even though this vaccine induced a specific immune response to HIV and proved to be effective in animal
models, we are not able to say whether it is effective in humans.
17. When will the Tat be put on the market?
The trial will take some years to determine whether the vaccine is safe and effective at preventing and/or curing
HIV/AIDS. If the efficacy will be confirmed, which will take several years, the vaccine could be registered and then
widely distributed.
18. Can I transmit the Tat vaccine or its effects to my partner or my family?
The immunity induced by this vaccine cannot be transmitted. It is worth to underline that a pregnant woman (or
someone planning to be) will not be allowed to volunteering in this phase, because of the unknown effects on the
fetus.Moreover, either men either women of child-bearing potential will have to adopt contraceptive methods of
proven efficacy during the immunization phase and for at least 6 months after its completion. .
19. If I participate in the Tat vaccine trial, will I test positive on an HIV test?
No, you will not. In HIV negative individuals, the Tat-based vaccine induces the production of anti-Tat specific
antibodies which will not give positive results in the diagnostic tests for HIV infection.
20. Does the Tat vaccine contain any quicksilver or squalene?
No, it does not.
21. Can anyone participate in the Tat vaccine trial?
No. Requirements to participate in the trial are specified in the clinical protocol. Depending on those requirements
(called inclusion criteria) an individual can volunteer for the trial. Inclusion criteria have been determined by a
group of researchers and doctors with the aim of easily understand trial results.
22. Can foreign (not Italian) people participate in the Tat vaccine trial?
Yes, they can, given that:
a) they have a regular permission to stay in the Country and identification documents;
b) they understand the Italian language and, therefore, they can declare to clearly understand the meaning of
what is written in the informed consent form.
23. Can people addicted to illicit drugs, alcoholics and/or psychotropic drugs participate in the Tat
vaccine trial?
No, they cannot. Participation in the trial is not allowed to drug and/or alcohol addicted people.
24. What do I have to do if I decide to participate in the Tat vaccine trial?
You have to go to one of the involved clinical sites, where they will describe you the trial procedures. In case you
confirm your willing to enrol, you will attend clinical, laboratory and psychological tests to assess your suitability
for the trial.
25. Is it dangerous if I decide to withdraw from the Tat vaccine trial before the completion of the
vaccination program?
No, it is not. To date, there is no evidence of health risk if the vaccination program is prematurely halted.
26. If I decide to take part in the Tat vaccine trial, what will they administer to me and how?
Clinical trial ISS T-002, currently under activation, is open label. This means that every participant is aware of
what he/she has been administered since the very beginning, depending on the arm he/she has been randomly
assigned. There will be no patients receiving placebo .
27. Does participating in a phase of the Tat vaccine trial give the right to take part in the subsequent
phase?
No, it does not. It is not possible to pass from a phase of the study to another.
28. How much does it cost participating in the Tat vaccine trial?
The vaccine is free as well as all the tests which will be conducted during the trial.
29. In case of side effects or adverse events occurring during the Tat vaccine trial, will volunteers be
compensated?
Yes, they will. A specific insurance policy for the Tat-based vaccine clinical trials has been taken out. It foresees a
compensation for damages caused directly by the vaccine.
30. Will the volunteers be refunded and/or paid for taking part in the Tat vaccine trial?
No, they will not. Italian law does not allow any remuneration for volunteering in clinical trials. No expense
allowance is foreseen.
31. Who will participate in the Tat vaccine trial will benefit of extra free days from work?
Volunteers have to verify with their employer whether there is the possibility of having extra free days from work,
according to their collective agreement.
32. Can volunteers stipulate an insurance policy? What do insurance companies foresee for whom has
drawn up an insurance policy and decides to participate in the Tat vaccine trial?
Insurance policies vary according to the insurance company, hence you should verify your policy conditions with
your agent.
33. Will people excluded from the phase I Tat vaccine trial be able to take part in the phase II Tat vaccine
trial?
Yes, they will. Individuals excluded from Phase I trial will be able to participate in Phase II trial whenever they
meet the inclusion criteria required for such phase.
34. Is there any medical benefit for the volunteers participating to the Tat vaccine trial?
There is no additional medical benefits for those who will participate in the trial in excess of those already
provided by the National Health System.
35. Who participates in the Tat vaccine trial will be able to keep on driving, drinking, smoking, exercising,
etc.? Will they have any limit in their daily life? Will they be able to keep animals at home? Will they be
able to travel without any limitations?
People participating in the trial are not requested to change their daily life in any way.
36. Participating in a Phase II trial will allow me to have unprotected sex with an HIV partner in the future?
No, it will not. The efficacy of the candidate vaccine has not been demonstrated yet. We will have results on the
efficacy of the vaccine only after completion of the Phase III trial.
37. Will an HIV positive woman be able to have a healthy child after having received the Tat vaccine?
Specific trials will have to be conducted to have indications about the efficacy of this vaccine in the maternalfoetal transmission. However, this kind of study can be started only after the completion of Phase I and II trials in
adults.
38. How can I enrol in the Tat vaccine trial?
If you wish to participate in the trial, you may refer to one of the clinical sites listed in the web site:
http://www.iss.it/aids/, or call the Toll Free AIDS number of the Istituto Superiore di Sanità (+39 800 861 061) from
10.00 a.m. to 6.00 p.m. until December 10th 2010, and, after this date, from 1:00 p.m. to 6:00 p.m.
39. If I enrol in the Tat vaccine trial, will I have to talk to my doctor?
Participating in a trial does not exclude basic medical care. It is important to keep on visiting your own doctor
when you take part in a trial. In case of volunteering, you will be given a letter that you might deliver to your family
doctor to inform him/her about the experimental treatment you have been administered.
40. Is the Tat vaccine dangerous? Are you already aware of any side effects?
The studies in animal models and Phase I trial in humans have not showed any toxic effects and the vaccine
seems to be safe. Nevertheless, it can induce pain, redness or swelling at the injection site. These side effects
are common to many vaccines, however the presence of rare and infrequent side effects can be evaluated only
after the subsequent trial phases.
41. Can people affected by other diseases participate in the Tat vaccine trial?
The doctors at the clinical site will be responsible to assess whether volunteers are suitable for the trial. Eligibility
determination will depend on the results of physical and instrumental examination, blood testing, and on medical
history and psychological assessment.
42. Will there be more than one administration of the Tat vaccine?
Usually more than one administration is needed to induce a satisfying immune response. The optimum number of
immunizations (administrations of the vaccine candidate) is still under experimental testing. ISS T-002 trial
foresees 2 treatment groups, with 3 or 5 immunizations, respectively. There will be no patients receiving placebo.
Further details will be provided by the doctor at the clinical sites during the interview prior to the possible trial
enrolment.
43. How many people will participate in the Tat vaccine trial?
One hundred and sixty (160) patients will be enrolled in the ISS T-002 trial.
44. If I participate in the Tat vaccine trial, am I protected from infection with HIV? Can I engage in risk
behaviors without concerns?
No, you cannot. We don't know whether this vaccine protects against HIV yet. Hence, the volunteer has to avoid
risk behaviors (for instance: unprotected sexual practice, no syringe exchange).
45. If I decide to take part in the Tat vaccine trial, can I change my mind later on?
Patients can withdraw at any time without any negative consequences.
46. If I decide to take part in the Tat vaccine trial, will anyone know about my participation?
Only the authorized medical staff (doctors, nurses) will know about your participation in the trial. All information,
personal or sensitive data concerning your identity will be identified only by an alphanumeric code and treated in
a way to protect privacy, confidentiality and security, in compliance with the in force legislation on the matter of
personal data processing. Only the authorized personnel can link this code to the participating patients.
47. What are the effects of Tat vaccination?
The data obtained at 48 weeks from the ongoing phase II clinical trial indicate that the Tat vaccine, administered
to HIV infected HAART-treated individuals with suppressed plasma viremia, is capable of restoring the
homeostasis, that is the proper equilibrium, of the immune system, which is heavily compromised by HIV
infection, thus optimizing and intensifying the effects of antiretroviral drugs.
48. On the basis of the results recently published in PLoS ONE, can one say that the Tat vaccine is
effective?
The results of the phase II study indicate that the Tat vaccine, used in association with the antiretroviral therapy in
patients with suppressed plasma viremia, reduces the immune activation in a selective and targeted manner, and
improves the immune function in HIV-infected patients. Further studies will be needed to determine whether the
Tat vaccine may be effective in the different clinical stages of HIV disease.
49. Can the Tat vaccine replace the antiretroviral therapy?
This is not known at present. Additional studies are needed to give an answer to this question. In this phase II
study the Tat vaccine has been tested on HIV-infected HAART-treated individuals with suppressed plasma
viremia. Therefore, the subjects immunized with the vaccine continued to take the antiretroviral drugs. The
synergistic effect of vaccination and antiretroviral treatment is the subject of the scientific publication in PLoS
ONE.
50. How many patients have received the Tat vaccine?
In the study published in PLoS ONE the vaccinees are 87. Considering also the previous phase I trial, a total of
114 HIV+ patients have been vaccinated with Tat so far. Nevertheless the phase II study is still ongoing and the
number of Tat immunized individuals is growing.
51. Which are the main benefits of the Tat vaccine?
Tat vaccine administration induces a significant improvement of several clinical parameters such as an increase
of CD4+ Tcell and B cell number, as well as a reduction of immune activation markers (i.e. the presence on the
cell surface of the CD38 molecule and the beta2-microglubina or neopterin levels, which are serum proteins
increased during inflammation and immune activation).
52. Which are the main results of the phase II trial?
The data of the phase II trial obtained so far indicate that Tat vaccination is safe and induces a specific and
durable immune response against Tat, which, by operating in synergy with the antiretroviral treatment, contributes
to the restoration of the proper equilibrium of the immune system that HAART alone is often unable to reestablish.
53. Where does the Tat vaccination operate?
The present data indicate that Tat vaccine acts on the immune activation and regulation, restoring the proper
behavior of the cells of the immune system. It is likely that, thanks to Tat vaccination, the risks of developing
those novel and serious diseases associated with the immune activation and dysregulation, which HAART cannot
overcome, are considerably reduced.
54.What is the immune activation?
It is like a “continuous alarm” of the immune system that seems to be consequent to the HIV persistence in those
cells/sites (the so called “sanctuaries”) in which it resides and resists to therapy.