US scientist Louis Picker announced encouraging results from a big monkey trial at AIDS Vaccine 2009 in Paris this morning.
The study found that 54% – 13 of the 24 rhesus macaques monkeys infected with SIV – showed complete control of infection after an initial viral “blip”.
And significantly for vaccine researchers, this research identified the type of immune cells with the capacity to completely suppress the monkey version of HIV (known as SIV).
The effector memory T-cells (CD8+ T-cells) seem to be powerful at blocking SIV at the early stage of infection as the virus enters the body.
This is a critical time for the body’s immune defence against HIV, as Dr Alan Bernstein, executive director of the HIV Global Vaccine Enterprise, explains: “It looks like the body has a narrow window of opportunity to stop HIV of hours up to a day or two.”
Picker said the cytomegalovirus (CMV) was known to be the best at triggering effector site-based T-cells. His team made three versions of a SIV vaccine using a modified form of CMV as the vector (vehicle to take virus particles into the body).
The form of CMV he used was replication competent vector (which means it can copy itself) and so far only non-replicating vectors have been used in human trials since they are safer.
Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said scientists did not know if a non-replicating vector could produce these results and this was the “big punch” in Louis’s results.
A smaller study of this last year found that his type of vaccine protected a third of the 12 monkeys on which it was tested.
The results announced today are more significant since it is a bigger trial and all three groups showed “robust” responses, confirming that effector memory T-cells are providing protection (are the correlates of protection).
Picker said: “The effector memory control was abrupt (immediate), seemingly stable and correlates to CD8+ T-cells.”
The way in which the immune responses protect the body is a major, and complex, question for HIV researchers.
Bernstein said: “This reseach is very important for two reasons: understanding the correlates of protection is critical and we should be looking to see if effector memory T-cells were activated in the Thailand and STEP trials.”
Scientists do not yet know how the RV144 vaccine tested in Thailand provided partial protection (31%). The standard assays (lab tests) they do to test immune strength were discouraging yet the vaccine had some positive results – so they must now discover why.
Picker said an effective vaccine could combine neutralising antibodies, plus a CMV vector, and prime-boost vaccine (to boost the effect).
He is director of the vaccine programme at the Oregon Health and Science University’s Vaccine and Gene Therapy Institute in the US.