Pauline E. Crewther

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The production of mature germ cells capable of generating totipotent zygotes is a highly specialized and sexually dimorphic process. The transition from diploid primordial germ cell to haploid spermatozoa requires genome-wide reprogramming of DNA methylation, stage- and testis-specific gene expression, mitotic and meiotic division, and the histone-protamine(More)
Apical membrane antigen 1 (AMA1) is considered one of the leading candidates for inclusion in a vaccine against blood stages of Plasmodium falciparum. Although the ama1 gene is relatively conserved compared to those for some other potential vaccine components, numerous point mutations have resulted in amino acid substitutions at many sites in the(More)
We describe an approach for the rapid mapping of epitopes within a malaria antigen using a combination of phage display techniques. Phage display of antigen fragments identifies the location of the epitopes, then random peptide libraries displayed on phage are employed to identify accurately amino acids involved in the epitope. Finally, phage display of(More)
Autoimmune regulator (AIRE) is an important transcription regulator that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags in the thymus. Although several mouse models of Aire deficiency have been described, none has analyzed the phenotype induced by a mutation that emulates the common 13-bp deletion in(More)
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is an autoimmune disorder caused by mutations in the autoimmune regulator gene AIRE. We examined the expression of Aire in different organs (thymus, spleen, and lymph nodes) in C57BL/6 mice, using a novel rat mAb, specific for murine Aire. Using flow cytometry, directly fluorochrome-labeled mAb(More)
Apical membrane antigen 1 (AMA-1), an asexual blood-stage antigen of Plasmodium falciparum, is an important candidate for testing as a component of a malaria vaccine. This study investigates the nature of diversity in the Plasmodium chabaudi adami homolog of AMA-1 and the impact of that diversity on the efficacy of the recombinant antigen as a vaccine(More)
A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 microg, 20 microg or 80 microg of AMA1, respectively, in 0.5 mL of(More)
Several new aspects of the chemistry, genetics and cellular distribution of the murine Qa-2 alloantigen were apparent in an analysis of this antigen using monoclonal antibodies recognizing a Qa-2-like antigen called Qa-m2. Immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis identified the Qa-m2 alloantigen as a(More)
The Plasmodium merozoite surface antigen apical membrane antigen-1 (AMA-1) has previously been shown to provide partial protection to Saimiri and rhesus monkeys immunised with recombinant Plasmodium fragile or parasite-derived Plasmodium knowlesi AMA-1, respectively. In the study reported here we have used the Plasmodium chabaudi/mouse model system to(More)
We showed previously that the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum contains a repetitive amino acid sequence. We have investigated here the sequence and antigenic relationships between RESA from FC27, a Papua New Guinea isolate, and from NF7, a Ghanaian isolate. The complete nucleotide sequences of eight different cDNA(More)