Modulation of HIV-1 immunity by adjuvants

Moody, M. Anthony

At present, the data to drive rational choices of adjuvants for an AIDS vaccine are lacking. This is partly because of the lack of a robust immunogen, but it is also because of the paucity of comparative data being published. In the last decade, few headto-head comparisons of adjuvant formulations using the same HIV-1 immunogen have been reported, especially when compared with the first 20 years of the AIDS pandemic (Table 1) . A partial reason for this is that adjuvants are not licensed by themselves but only as part of the licensure of a vaccine product. That is an entirely appropriate regulatory hurdle, but it does mean that an adjuvant licensed or on track for licensure combined with a vaccine for a non-HIV pathogen could be put at risk. If an adjuvant is found to be superior for an HIV-1 vaccine candidate, by definition other adjuvants will be inferior for that HIV-1 vaccine. This does not mean that an adjuvant inferior for an HIV-1 vaccine is inferior for all other vaccines, nor would it render a licensed vaccine ineffective. However, it would create a perception that one company's adjuvant is 'better' than the others, putting vaccines using the 'inferior' adjuvants at risk. Given that the vaccine market is small compared with blockbuster drugs [95] , companies appear to be appropriately reluctant to put their investments at risk. In addition, other hurdles face adjuvant development. As preventive measures, vaccines should be well tolerated for the general population and ideally cause no side-effects to anyone. As vaccines require stimulation of the immune system, establishing a balance between stimulation and side-effects is paramount (Fig. 1) . However, no medical intervention is without risk and it is likely that a successful vaccine will cause some degree of side-effects in some recipients, and it will be important to determine the level of acceptable risk that balances with vaccine efficacy. Public judgment of acceptable risk will depend on vaccine efficacy, that is, a highly effective vaccine against a present threat that has some side-effects will likely be more acceptable than a vaccine that is less effective or is against a pathogen perceived to be less of a threat. Until an effective HIV-1 vaccine is available, work to find better adjuvants should continue.