Induction of phosphocholine-specific antibodies in X-linked immune deficient mice: in vivo protection against a Streptococcus pneumoniae challenge

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Abstract
X-linked Immune deficient (XID) mice are susceptible to infection with Streptococcus pneumoniae because they fail to mount an immune response to the Immunodomlnant phosphochollne (PC) epltope on the bacterial cell wall. It is difficult to induce PC-speclflc antibodies in XID mice because PC-specific B cells expressing the T15-, M167- and M603 Idiotype (Id), which provide protection against S. pneumoniae, are deleted in these mice via an antigen-specific, receptor-mediated process. In addition, the standard PC hapten, p-dlazophenylphosphochollne (DPPC), induces high affinity phenylphosphochollne (PPC)-speciflc antibodies in XID mice, which are not protective against S. pneumoniae. We have used a novel PC hapten, p-nitrophenyl-6-(O-phospho-choline)hydroxyhexanoate (EPC), to induce PC-specific antibodies in XID mice. The immune response to EPC-keyhole limpet hemacyanln (KLH) is dominated by IgGi, VH1+, US-Id−, PC-inhlbitable antibodies. A small IgM antl-PC response having a consistent T15-ld+ component is also induced in XID mice, whereas normal mice produce a large IgM response dominated by T15-ld+ antibodies. The immune response to EPC-KLH remains predominantly PC-lnhlbltable even after multiple immunizations, while the response to DPPC–KLH becomes dominated by PPC-speclflc antibodies. C.CBA/N mice immunized twice with EPC–KLH are protected against 104S. pneumoniae while as few as 10 bacteria are 100% lethal for the unlmmunlzed controls. The ability of EPC-protein to induce a long-lived, PC-speclflc response should make this hapten a potential TD vaccine candidate for S. pneumoniae

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