If pneumococcal conjugate vaccines (PCV) are to be introduced in developing countries where HIV prevalence can reach over 30% researchers must begin to understand how HIV changes the vaccination picture and whether vaccines are even an effective option in HIV-infected individuals. Studies here show that this research is already underway.

A small pilot study by Neil French and colleagues looked at the effects of PCV in HIV-infected Malawian adults untreated with antiretroviral therapy (see poster PSV-21). They found that PCV was well-tolerated with minimal side effects and saw no gross change in either viral load or CD4 T-cell counts. Underlining the importance of pneumococcal vaccine research in adults in high HIV-prevalence areas, Dr. French says, “HIV-infected cases make up 50-90% of all adult pneumonia in these settings. If we are considering pneumococcal vaccines we must consider HIV.” A large clinical trial is now underway to investigate whether the vaccine protects HIV-infected adults against pneumococcal disease. Dr. French cautions, “we saw no effect in this population using polysaccharide vaccines and have doubts that we will see an effect using the conjugate vaccine. In devising a way to effectively vaccinate these adults conventional vaccine thinking is not enough. This is why I believe basic science research is so important in this area.”

A large, randomised controlled vaccine trial of children in South Africa done by Shabhir Madhi and colleagues looked at the efficacy of PCV in HIV-infected children (see poster PSV-34). Although they did see a reduction in vaccine serotypes, overall vaccine efficacy decreased in these children as compared to HIV-uninfected controls. This difference in efficacy is attributed to serotype replacement.

Both of these trials highlight the need for further innovative research to identify effective means of protecting both HIV-infected children and adults from pneumococcal disease.

Data presented at ISPPD-4 indicate that pneumococcal vaccine research is alive and well. Researchers in the field continue to push the envelope in looking for better ways to do everything from creating more efficacious vaccines to exploring alternate vaccine delivery patterns. Three studies highlighted here illustrate this innovation.

One limiting factor in vaccination is just how many injections children are willing and able to endure. Van Dijken and colleagues addressed this problem by studying the efficacy of a combination pneumococcal/Men C conjugate plus HexaMen vaccine in mice (poster PSV-17). Such a vaccine would protect against pneumococcal disease as well as meningitis B and C. The authors found not only that combining the vaccines did not have a negative effect on immunogenicity, but that the vaccine was in fact more efficacious. This increase in efficacy is probably due to lipopolysaccharides in HexaMen acting as adjuvants.

As many are aware, right now the pneumococcal conjugate vaccine can be prohibitively expensive for many poor countries. In relation to this problem Punmalainen and colleagues examined the immunogenicity of a single dose 11-valent PCV as compared to the usual three dose regimen (see talk PSV2-03). Interestingly the authors found similar persisting antibody concentrations and functional activities in both groups. If proven effective in prevention of pneumococcal disease this alternative dose regimen could have very positive implications for vaccination in economically constrained countries.

One obvious constraint in pneumococcal vaccine development is the issue of multiple serotypes and the difficulty in protecting against enough of them so as to prevent disease. One potential solution to this problem would be a non-toxic pneumolysin protein used in conjugation to confer serotype non-specific protection against pneumococcal disease. But until now this has proven elusive as PLY is highly toxic, both in vitro and in vivo. Now Kirkham and colleagues have developed a non-toxic mutant pneumolysin (PLY) (see poster PROT-17). This development could lead to better protection against pneumococcal disease.