Articles of Significant Interest Selected from This Issue by the Editors

doi:10.1128/IAI.01387-07

DOI: 10.1128/IAI.01387-07

Survival Studies without Evaluation of Microbial Burden Can Be Misleading

A vaccine candidate used in studies of protection against murine pulmonary coccidioidomycosis is a parasitic cell wall-associated, proline-rich protein designated Ag2/Pra. Herr et al. (p. 5777-5787) showed that vaccination of C57BL/6 mice with recombinant Ag2/Pra plus CpG (adjuvant) failed to reduce the fungal burden in lungs of the intranasally challenged animals. However, when recombinant Ag2/Pra was combined with another homologous member of the family of proline-rich proteins, significantly better clearance of the pathogen was observed. Enzyme-linked immunospot assays revealed that the two immunogenic homologs contain unique T-cell epitopes and in combination stimulate a more heterogeneous and protective T-cell repertoire than the monovalent vaccines.

Distinct Dendritic Cell Responses Correlate with Human Susceptibility to Haemophilus ducreyi Infection

The current understanding of dendritic cell (DC) responses to pathogens is that phylogenetically distinct pathogens cause unique transcript responses. Person-to-person variation in responses to one organism has been noted, but its significance was unclear. Humphreys et al. (p. 5686-5697) show that DCs obtained from volunteers who form abscesses after inoculation with Haemophilus ducreyi have transcript responses to the organism that differ from those from volunteers in whom infection spontaneously clears. Similar observations were made for infected tissues from the two groups. These findings highlight the importance of variation in DC responses in shaping successful and failed immune responses in humans.

Studies of Interactions between Bacterial Pathogens and Human Cells Advanced by the Use of Peptide-Major Histocompatibility Complex Tetramer Technology

Peptide-major histocompatability complex (pMHC) tetramer technology is widely used to identify and characterize T cells expressing specific viral antigens. Massey et al. (p. 5711-5715) describe the use of this technology to study proteins secreted by the bacterial pathogen Staphylococcus aureus that are believed to interfere with human cells. They demonstrate that this technology can be used to study the activity of superantigens, such as the toxic shock syndrome toxin, which nonspecifically crosslinks MHC and T-cell receptor (TCR) molecules. They also find that despite structural and amino acid sequence similarities to known proteins, the S. aureus Eap protein does not block MHC:TCR interactions and is not a superantigen. These findings demonstrate that pMHC technology is a valuable in vitro tool for the study of bacterium:human interactions.

Fine Specificity of Anti-Plasmodium falciparum Apical Membrane Antigen 1 Antibodies Depends on Species Immunized

Although apical membrane antigen 1 (AMA1) is a major blood stage malarial vaccine candidate, allelic polymorphism of the AMA1 gene is a potential hurdle for vaccine development. Miura et al. (p. 5827-5836) demonstrated that, in contrast to single allelic immunization, a mixture of two AMA1 alleles elicits primarily cross-reactive antibodies in rabbits, as judged by growth inhibition assay (GIA). In contrast, sera from monkeys failed to distinguish the two alleles when tested by GIA. Thus, AMA1 proteins induced different specificities of functional antibodies depending on the animal species immunized, suggesting that polymorphism of AMA1 alleles may not be an insurmountable problem to successful vaccine development.