Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci

Nina D. Russell, Jose R.F. Corvalan, Michael L. Gallo, C. Geoffrey Davis, Liise Anne Pirofski

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Infections with Streptococcus pneumoniae remain a significant cause of morbidity and mortality. To gain insight into structure-function relationships for human antibodies to pneumococcal capsular polysaccharide (PPS), we studied the response of transgenic mice reconstituted with human immunoglobulin loci, XenoMouse, to PPS antigens in a pneumococcal vaccine. Enzyme-linked immunosorbent assays of sera from mice vaccinated with a 23- valent pneumococcal vaccine revealed that they produced serotype-specific human antibodies, with the greatest response being to the PPS of serotype 3 (PPS 3). Molecular sequence analysis of three monoclonal antibodies (MAbs) to PPS 3 generated from lymphoid cells from mice vaccinated with a 23-valent pneumococcal vaccine or a PPS 3-bovine serum albumin conjugate revealed that they all used heavy-chain immunoglobulin genes from the V(H)3 family, two expressed light chain genes from the human Vκ1 family, and one expressed a mouse λ light chain. The protective efficacy of the two MAbs was examined in mice. A 10-μg dose of both, and a 1-μg dose of one, significantly prolonged survival from a lethal serotype 3 infection in CBA/N mice. Our data show that XenoMouse mice produced protective, serotype-specific human antibodies to PPS 3, and they lend support to the proposal that these animals represent a useful model to study the human antibody response to PPS antigens.

Original languageEnglish (US)
Pages (from-to)1820-1826
Number of pages7
JournalInfection and immunity
Volume68
Issue number4
DOIs
StatePublished - Apr 2000

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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