Pneumococcal surface protein A (PspA), a cross-reactive protein expressed by all pneumococci, is known to elicit an antibody in animals that can passively protect mice from infection with Streptococcus pneumoniae. A phase I trial with recombinant PspA showed the protein to be immunogenic in humans. Pre- and postimmune serum samples from this trial were examined, and human antibody to PspA could protect mice from pneumococcal infection. The serum samples of subjects immunized twice with 125 microg of PspA had >100 times as much antibody per milliliter as was required to consistently protect mice from fatal infection (1.3 microg/dose). At least 98% of PspAs fall into PspA sequence/serologic families 1 or 2. Human antibodies elicited by a family 1 PspA protected against infection with S. pneumoniae expressing either family 1 or 2 PspAs and with strains of all 3 capsular types tested: 3, 6A, and 6B. These studies suggest that PspA may have efficacy as a human vaccine.

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Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4+ T helper (Th) cell subset. While several factors contribute to the development of CD4+ Thi and Th2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a Th2 to a Thl response. The data suggest that decreasing antigen levels may be required for to inhibit a Th2 response and enhance a Thi response.

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