Abstract: The present invention provides an attenuated hepatitis A virus useful as a vaccine.

Abstract: Modified Pseudomonas exotaxins which comprise deletions in at least domain 1A are taught. The toxins exhibit reduced cytotoxicity.

Abstract: The circumsporozoite (CS) protein of Plasmodium falciparum has been analyzed to develop a new anti-sporozoite malarial vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high titer antibody response was formed. This peptide sequence is capable of priming helper T-cells for a secondary response to the intact CS protein. This site represents the first helper T-cell site described for the CS molecule outside of the repetitive region, and is a major immunodominant T-site on the molecule. The approach described herein is useful in the rational design and construction of more efficacious vaccines.

Abstract: The complete nucleotide sequence of the pertussis toxin gene and the deduced amino acid sequences of the individual subunits have been determined. All five subunits are coded by closely linked cistrons and possibly expressed through a polycistronic mRNA, since a promotor-like structure was found in the 5' flanking region. The order of the cistrons is S1, S2, S3, S4, S5, and S3. All subunits contain signal peptides of variable length. The calculated molecular weights of the mature subunits are 25,024 for S1, 21,924 for S2, 21,873 for S3, 12,058 for S4 and 11,013 for S5. All subunits contain signal peptides of variable length. Subunits S2 and S3 share 70% amino acid homology and 75% nucleotide homology. Subunit S1 contains two regions of eight amino acids homologous to analogous regions in the A subunit of both cholera and E. coli heat labile toxins. Functional domains in relation to the primary structure and the development of a safer, new generation vaccine against whooping cough are presented.

Abstract: The present invention discloses several DNA mutagenesis processes using a DNA template containing several uracil residues in place of thymine, which can be applied without selection techniques to produce altered DNA sequences with approximately 10-fold greater efficiency than current methods of site-specific mutagenesis.This template has relatively normal coding potential in the in vitro reactions typical of standard site-directed mutagenesis protocols but is not biologically active upon transfection into a wild type (i.e., ung.sup.+) E. coli host cell. Expression of a desired change, present in the newly synthesized non-uracil-containing covalently closed circular complementary strand, is thus favored. The procedure has been applied to mutations introduced via both obligonucleotides and error-prone polymerization. The inclusion of two additional simple treatment steps before transfection results in a site-specific mutation frequency approaching 100%.