The Phase I of the country’s first AIDS vaccine trial conducted at the National AIDS Research Institute (NARI), Pune, has been completed successfully. However, the Adeno-associated virus (AAV) vaccine will not undergo further testing.
The International AIDS Vaccine Initiative (IAVI), a New York based NGO has decided not to test AAV vaccine any more in any country.
Though the Adeno-associated virus (AAV) used as a vector in the vaccine trial has been found to be safe and well tolerated, the vaccine has not been able to elicit acceptable immune response in those who received the vaccine.
“IAVI [International AIDS Vaccine Initiative] has completed its clinical testing of the AAV vector and at present has no plans to test it further,” said Dr. Sonali Kochhar, Medical Director, IAVI India Programme, Delhi.
“The AAV …met safety criteria, but it did not induce immune responses in a sufficient number of the volunteers to meet the criteria for advancement.” The trial was conducted on 30 volunteers who were split into three groups of 10 each. Of the ten, eight received the vaccine and two got a placebo (dummy).
The grouping was done to test three different doses of the vaccine — the lowest vector particle dose was 3×10{+9} and the highest dose was 3×10{+1}{+1}.
The Phase I trial in Pune showed that the immune response was about 20 per cent even in those who received the highest dose.
While some feel that a first generation vaccine with an immune response of 30 per cent would be good enough, Dr. Kochhar, in an email to this correspondent, noted that it is not known “… what [level of] immune response will convey protection. IAVI looks for at least 60 per cent immune responses before moving forward toward tests for efficacy.”
The decision not to test AAV vaccine anymore is not based on the results from India alone. AAV vaccine was tested in Belgium and Germany, apart from five sites in Africa.
The results of the Belgium and Germany trials were similar to that of India — 20 per cent immune response.
Unlike in India, volunteers in Belgium and Germany received a booster dose of 3×10{+1}{+1}, the highest dose used in the trials.
But the booster dose “did not improve the immune response significantly.”
Volunteers in Africa received a highest vector particle concentration of 3×10{+1}{+2} compared with 3×10{+1}{+1} in India. They also received a booster dose. But the results were not encouraging.
“There is a modest increase in the immune responses seen with the higher doses. The booster did not result in immune responses that were considered adequate to carry this product forward for efficacy testing,” Dr. Kochhar noted.
The trial carried out in three continents showed that neither a booster dose nor increased dose concentration produced significant improvement in immune response.
In short, AAV vaccine did not justify testing the vaccine for efficacy.
The setback comes despite the vaccine producing high immune response in non-human primates at doses given to humans.
It must, however, be remembered that not all drugs or vaccines proceed from Phase I to Phase II and III trials.
According to a senior official at NARI, despite the decision not to proceed further with the trials, the vaccine has been found to be safe, and more importantly, the trial has showed that it is indeed possible to recruit, retain and follow up on HIV-uninfected volunteers for one year.
The trial has shown that Indian scientists and institutions are equipped to test AIDS vaccines in an ethical manner.