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Attributes of a successful vaccine
Vaccine safety
The first requirement for an HIV preventive vaccine must be a high level of safety, both for people who are HIV-negative and for people who are HIV-positive.
To maximise public health benefit, it will probably be necessary to aim for universal immunisation of children before they become sexually active. This implies the need for a level of safety comparable to other widely used vaccines given to children throughout the world. One strategy under consideration is to include components from HIV in a widely-used live vaccine against measles, which generates long-lasting immunity when given to young children and can be boosted in adolescence.
An HIV vaccine needs to be safe for HIV-positive individuals because universal HIV testing may not be feasible before administering a vaccine.
These considerations have favoured the use of vaccines based on relatively small fragments of HIV. Where these vaccines use other viruses to present these HIV elements to the immune system, there has been a preference for viruses that cannot replicate freely in human cells. However, some experts now believe that a stronger vaccine system will be needed to achieve protection against HIV.
Safety depends on a manufacturing process that is well understood and can be closely controlled, even when undertaken on a very large scale, and on a preparation that does not deteriorate during storage and transport and which is safe to administer.
Vaccine effectiveness
The primary aim of vaccination is to prevent disease. This may, or may not, require the prevention of infection. Typically, vaccines do not prevent infection with the organism against which they are directed, but prompt a rapid and effective immune response that clears or controls it, or prevents it from causing serious harm.
In the case of an HIV vaccine, considerable public health benefit could be obtained from a vaccine which delayed the onset of disease by reducing viral load, especially if it cut the chance of onward transmission in people who became infected with HIV despite vaccination.
The only way to evaluate the effectiveness of an HIV vaccine is through field trials. Typically, the vaccine would be administered to large numbers of people at high risk of infection. After a certain time period, the vaccinated participants' experiences are compared to those of people who received a placebo (a dummy vaccine). It is a basic ethical requirement that all trial participants have access to existing means of prevention, including education and counselling, and are not disadvantaged medically or socially through their participation.
Once there is evidence of human protection, animal studies and laboratory measurements of human immune responses may be used to determine which immune responses are correlated with protection against HIV infection. This may help to speed up further research and development. Unfortunately, some researchers talk as though these 'correlates of protection' can be established in advance of actual human protection studies: this is not the case.
Nevertheless, there will be much greater interest in vaccines that are shown to be capable of inducing consistently measurable and potentially relevant immune responses than in those that are not. Among the questions that are asked of a candidate vaccine are:
It may be that 'yes' to one or two of these would be enough, in practice, to protect most people, most of the time, from most HIV exposures. It may also be that protection against HIV could be induced in another way entirely. It may be that two or more vaccines working in completely different ways would be equally capable of protecting against HIV.
Global accessibility
Whether an effective, safe vaccine will actually be provided to those in need of it depends on more than technical factors. However, some technical characteristics may help or hinder widespread use of any vaccine:
The ideal vaccine would only need one dose to provide lifelong protection. However, if HIV vaccination can be integrated with the delivery of other vaccines and healthcare over an individual's lifetime, then even a requirement for multiple immunisations need not prevent widespread access.
In practice, other economic and commercial factors, especially the need for pharmaceutical companies to recoup their costs through exploiting temporary monopolies on patents, create greater barriers to access than any of the technical factors listed. However, even in this area creative solutions are possible such as pricing vaccines at different levels for use in different countries, as is common practice for existing vaccines.
The first requirement for an HIV preventive vaccine must be a high level of safety, both for people who are HIV-negative and for people who are HIV-positive.
To maximise public health benefit, it will probably be necessary to aim for universal immunisation of children before they become sexually active. This implies the need for a level of safety comparable to other widely used vaccines given to children throughout the world. One strategy under consideration is to include components from HIV in a widely-used live vaccine against measles, which generates long-lasting immunity when given to young children and can be boosted in adolescence.
An HIV vaccine needs to be safe for HIV-positive individuals because universal HIV testing may not be feasible before administering a vaccine.
These considerations have favoured the use of vaccines based on relatively small fragments of HIV. Where these vaccines use other viruses to present these HIV elements to the immune system, there has been a preference for viruses that cannot replicate freely in human cells. However, some experts now believe that a stronger vaccine system will be needed to achieve protection against HIV.
Safety depends on a manufacturing process that is well understood and can be closely controlled, even when undertaken on a very large scale, and on a preparation that does not deteriorate during storage and transport and which is safe to administer.
Vaccine effectiveness
The primary aim of vaccination is to prevent disease. This may, or may not, require the prevention of infection. Typically, vaccines do not prevent infection with the organism against which they are directed, but prompt a rapid and effective immune response that clears or controls it, or prevents it from causing serious harm.
In the case of an HIV vaccine, considerable public health benefit could be obtained from a vaccine which delayed the onset of disease by reducing viral load, especially if it cut the chance of onward transmission in people who became infected with HIV despite vaccination.
The only way to evaluate the effectiveness of an HIV vaccine is through field trials. Typically, the vaccine would be administered to large numbers of people at high risk of infection. After a certain time period, the vaccinated participants' experiences are compared to those of people who received a placebo (a dummy vaccine). It is a basic ethical requirement that all trial participants have access to existing means of prevention, including education and counselling, and are not disadvantaged medically or socially through their participation.
Once there is evidence of human protection, animal studies and laboratory measurements of human immune responses may be used to determine which immune responses are correlated with protection against HIV infection. This may help to speed up further research and development. Unfortunately, some researchers talk as though these 'correlates of protection' can be established in advance of actual human protection studies: this is not the case.
Nevertheless, there will be much greater interest in vaccines that are shown to be capable of inducing consistently measurable and potentially relevant immune responses than in those that are not. Among the questions that are asked of a candidate vaccine are:
- Does a similar vaccine targeted against the simian immunodeficiency virus (SIV) protect rhesus macaques against SIV?
- Does the vaccine protect macaques from simian/human immunodeficiency virus (SHIV), or pigtail macaques from HIV-1?
- Does the vaccine induce neutralising antibodies in humans, i.e. antibodies capable of protecting cells from infection with HIV?
- Does the vaccine induce CD8 T-cell responses in humans, that are capable of killing HIV-infected cells?
- Does the vaccine induce human mucosal antibodies, for example, in the vagina or the rectum, which might protect against sexual infection?
- Does the vaccine induce a human CD4 T-cell response which can assist either in producing more effective cellular immunity or more effective antibodies? If so, will this outweigh any risk that a vaccine may set up more targets for HIV itself to infect? (Staprans 2004)
- Does the vaccine have a long-lasting effect, efficiently creating a population of 'memory' T-cells or B-cells?
- Are the immune responses active against a broad range of different HIV-1 strains found in different countries, such as the 'M' group subtypes (A to G) and groups 'O' and 'N'?
- Are the immune responses active against SIVs from chimpanzees?
- Are the immune responses active against virus strains adapted to use different co-receptors to gain entry to cells, especially those using CCR5 or CXCR4?
- Are the immune responses as strong against freshly-isolated viruses from people with HIV (primary isolates) as they may be against viruses that have been grown for a long time in cell-cultures (laboratory-adapted strains)?
It may be that 'yes' to one or two of these would be enough, in practice, to protect most people, most of the time, from most HIV exposures. It may also be that protection against HIV could be induced in another way entirely. It may be that two or more vaccines working in completely different ways would be equally capable of protecting against HIV.
Global accessibility
Whether an effective, safe vaccine will actually be provided to those in need of it depends on more than technical factors. However, some technical characteristics may help or hinder widespread use of any vaccine:
- Some vaccines are inherently cheaper and easier to make than others, although all should become cheaper as production is scaled up.
- Transport costs vary widely. Products which have to be refrigerated are much more expensive to deliver than those which are stable at higher temperatures.
- Products given by syringe are inherently more expensive than those which can be taken by mouth or as a nasal spray.
The ideal vaccine would only need one dose to provide lifelong protection. However, if HIV vaccination can be integrated with the delivery of other vaccines and healthcare over an individual's lifetime, then even a requirement for multiple immunisations need not prevent widespread access.
In practice, other economic and commercial factors, especially the need for pharmaceutical companies to recoup their costs through exploiting temporary monopolies on patents, create greater barriers to access than any of the technical factors listed. However, even in this area creative solutions are possible such as pricing vaccines at different levels for use in different countries, as is common practice for existing vaccines.