Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs.

A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with CpG and alum.

Influence of formulation pH and suspension state on freezing-induced agglomeration of aluminum adjuvants.

Freezing and thawing of vaccines containing aluminum adjuvants can lead to formation of aggregates and loss in vaccine potency. We sought to understand whether and to what extent the freeze-thaw damage to aluminum adjuvants would differ based on suspension state (flocculation and settlement) at the time of freezing. As flocculation and settlement characteristics of aluminum adjuvants are driven largely by the electrostatic charges on the adjuvant particles, which, in turn, are strongly influenced by the pH of the suspension, we conducted freeze-thaw studies on both Adjuphos and Alhydrogel™ samples at three pH levels (4, 6.

Stability of lyophilized human growth hormone.

To evaluate relationships between the extent of protein-excipient interactions, structural relaxation of an amorphous matrix, and the physico-chemical stability of a protein, human growth hormone (hGH) was lyophilized with sucrose and trehalose in a 1:2 weight ratio. The protein-excipient interactions were analyzed immediately after lyophilization with isoperibol solution calorimetry (ISC), water sorption analysis (WSA), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). The physical and chemical stability of hGH during storage at 50 degrees C was monitored by reverse phase (RP)-HPLC, SEC-HPLC and UV absorption spectroscopy.

Physical characterization of clostridium difficile toxins and toxoids: effect of the formaldehyde crosslinking on thermal stability.

Nosocomial diarrhea and pseudomembranous colitis causing toxins A and B from Clostridium difficile were studied at pH 5-8 and over the temperature range of 10-85 degrees C. The proteins were crosslinked with formaldehyde to inactivate them to toxoid forms and permit their use as vaccines. Structural changes and aggregation behavior were monitored with circular dichroism, intrinsic and extrinsic (ANS) fluorescence spectroscopy, turbidity measurements, high-resolution UV absorbance spectroscopy and dynamic light scattering.

Preformulation studies of Clostridium difficile toxoids A and B.

To enhance the physical stability of Clostridium difficile toxoids A and B, screening for stabilizing compounds was performed. The screening of 30 GRAS compounds at various concentrations and in several combinations was performed in two parts. First, a high-throughput aggregation assay was used to screen for compounds which delayed or prevented aggregation of toxoids under stress conditions (toxoids at pH 5-5.

Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity.

The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure-activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner-Wadsworth-Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B.