ABSTRACT
A DNA plasmid containing a chimeric sequence encoding both herpes simplex virus type 2 (HSV-2) glycoprotein B (gB) and glycoprotein D (gD) external domains (pcgDB) was used to immunize BALB/c mice against genital HSV-2 infection. To determine the efficacy of this vaccine, groups of mice immunized with the pcgDB plasmid were compared with animals immunized with plasmids corresponding to the individual proteins (pcgBt or pcgDt), administered separately or in combination (pcgBt + pcgDt). We studied the response of the different mouse groups to viral challenge by analyzing clinical disease (vaginitis), serum antibody levels, as well as lymphoproliferative responses and cytokine production by spleen cells. Increased IFN-gamma levels correlated with prolonged survival in mice immunized with the plasmid pcgDB, relative to mice immunized with plasmids coding for the individual proteins alone or in combination. Our results show that immunization with the plasmid encoding the chimeric protein is advantageous over separate proteins. These findings may have important implications for the development of multivalent DNA vaccines against HSV and other complex pathogens.
Subject(s)
Herpes Labialis/prevention & control , Herpes Simplex Virus Vaccines/immunology , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/immunology , Plasmids/immunology , Recombinant Fusion Proteins/immunology , Vaccines, DNA/immunology , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Animals , Cell Line , Cytokines/biosynthesis , Cytokines/genetics , Enzyme-Linked Immunosorbent Assay , Escherichia coli/metabolism , Female , Genetic Vectors , Herpes Labialis/immunology , Herpes Labialis/virology , Immunity, Cellular/immunology , Immunoglobulin G/analysis , Lymphocytes/immunology , Mice , Mice, Inbred BALB C , Precipitin Tests , Protein Biosynthesis/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , Spleen/cytology , Survival Analysis , Transfection , Vagina/virologyABSTRACT
We studied the in-vitro activity of HMR 3004 (RU 64004), a new ketolide, against 161 clinical isolates of Corynebacterium spp. including isolates resistant to erythromycin A, josamycin and lincomycin. HMR 3004 was active against all erythromycin A-sensitive isolates as well as against 75.8% and 45.4% of erythromycin A-intermediate and -resistant isolates, respectively. In contrast, HMR 3004 was active against 40 (46.5%) of 86 isolates resistant to erythromycin A, josamycin and lincomycin as well as against two isolates that were resistant to erythromycin A and lincomycin but not resistant (i.e. susceptible or intermediate) to josamycin.
