In two separate presentations at the AIDS Vaccine 04 meeting in Lausanne, Dr Frederic Tangy from the Agence Nationale de Recherches sur le Sida (ANRS) in Paris advocated the use of a licensed live attenuated measles vaccine – the very same one used in the measles, mumps and rubella (MMR) system given to millions of children – as a vehicle to deliver an HIV vaccine for future generations.
The proposal marked a welcome shift in the direction of serious consideration of how to make future HIV vaccines available to infants and adolescents – especially girls - who are, in many countries, the populations most desperately in need of protection against the epidemic. A Swiss company, Berna Biotech, has already made prototypes based on a live measles vaccine with HIV genes inserted, and a progress report on this work was also presented.
The vision would be that a child would be vaccinated from before the age of one and boosted at around the age of 10 to achieve a level of immunity that could and should last until adulthood. Adults with pre-existing immunity to measles – or at least those who have been previously vaccinated – could either receive repeated doses of measles-based vaccine or a prime-boost using measles with another vector, both containing HIV-related sequences.
The arguments put forward in support of this strategy include the excellent safety record of this live vaccine, its remarkable ability to offer long-term and boostable protection against disease, and that large-scale manufacturing facilities in several countries produce tens of millions of doses at extremely low cost. By inserting HIV-related sequences in one or more of three distinct locations in the vaccine strain, immunity to HIV could be induced in addition to protection against measles at no extra cost.
There are, however, one or two problems identified in the course of the meeting.
The first difficulty is that no-one knows precisely what components of HIV, and in what form, should be included in such a vaccine. The very long-acting effect of the measles vaccine could itself generate serious problems, if the wrong elements were added to it. At worst, children vaccinated in infancy might have inappropriate immune responses and would be unable to benefit as adolescents from a better vaccine that might by then be available to them.
The second problem is that the idea of using an established vaccine in this way would need to be discussed and agreed with stakeholders who are not currently involved in the AIDS vaccine effort and were not represented at the meeting in Lausanne. Given that millions of children in developing countries are still dying each year from measles, nothing should be done that could in any way undermine public confidence in the vaccine programme.
Measles is far from being eradicated, and mass vaccination with the live vaccine is therefore likely to continue for decades to come. However, the same is hopefully not the case for polio.
Some researchers would like to include HIV antigens in a version of the currently licensed live Sabin polio vaccine.They point to animal studies in which polio-vectored SIV components have been one of the very few systems shown to protect monkeys against some particularly virulent forms of SIV. The only comparable protection has been achieved with live attenuated forms of SIV itself, which is unacceptable as a prototype for HIV in the light of evidence that such viruses do, eventually, cause SIV-related disease.
This proposal flies in the face of moves in countries such as the United Kingdom to abandon live polio vaccine in favour of less potent but non-replicating vaccines given by injection. If the politics and other circumstances of the last refuges of the virus in Africa and Asia allow polio to be eradicated, will anyone really want to continue to use live polio vaccines? Those vaccines can – at a rate of less than one in a million – revert to forms that cause damage to the nervous system. It is claimed that with “high fidelity” variants of a key enzyme, this risk can be reduced. But since the only way to prove this would be through giving the vaccine to millions of people, will anyone ever be prepared to make the experiment, at the risk of re-introducing polio in a world where immunity to the disease would be waning fast?
Andino R. Polio vector – another strategy with a pediatric vaccine. AIDS Vaccine 04, Lausanne, abstract 76b, 2004.
Lorin C et al. Measles vaccine as a potential vector for AIDS vaccination. AIDS Vaccine 04, Lausanne, abstract 13, 2004.
Tangy F. Viral vectors overview. AIDS Vaccine 04, Lausanne, abstract 74, 2004.
Zuniga A et al. Live attenuated measles virus: a candidate vector for HIV vaccine. AIDS Vaccine 04, Lausanne, abstract 12, 2004.