Oral immunization with poly(lactide-co-glycolide) microparticles containing an entrapped recombinant glycoprotein (gD2) from herpes simplex type 2 virus

S.T.P. Pharma Sciences

Volumn 8, Issue 1, 1998, Pages 41-46

  Barackman, J D ^a   Singh, M ^a   Ugozzoli, M ^a   Ott, G S ^a   O'Hagan, D T ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Adsorption; Controlled release; Mucosal immunization; Poly(lactide co glycolide) microparticles; Protein stability; Vaccines

Indexed keywords

HERPES SIMPLEX VACCINE; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; POLYGLACTIN; RECOMBINANT PROTEIN; VIRUS GLYCOPROTEIN;

ADSORPTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY RESPONSE; DRUG RELEASE; DRUG STABILITY; ENCAPSULATION; HERPES SIMPLEX VIRUS 2; IMMUNIZATION; IMMUNOGENICITY; INTRAGASTRIC DRUG ADMINISTRATION; INTRAMUSCULAR DRUG ADMINISTRATION; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; REVIEW;

EID: 0031952788     PISSN: 11571489     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (39)

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32. ELISA plates (Nunc Maxisorb) were precoated with the anti-HSVgD2 MAb D10G12, a mouse monoclonal antibody developed at Chiron and used to qualitatively assess HSVgD2 conformational integrity and antigenic quality. High specific activities as measured by this antibody are associated with an intact tertiary structure and ability to generate neutralizing titers. After blocking (1% BSA, 3% sucrose in PBS) and washing with water, wells were coated with 1/3 serially diluted HSVgD2 standards and microsphere release supernatants at an initial HSVgD2 content of 200 ng/ml (based on BCA) using dilution buffer (1% BSA, 0.3% Tween 20 in PBS). Plates were washed with wash buffer (0.3% Tween 20 in PBS), then coated with polyclonal rabbit anti-HSV2 (DAKO). Plates were washed with wash buffer then coated with goat anti-rabbit IgG-HRP conjugate (Tago) and developed with TMB substrate (Kirkegaard and Perry Laboratories). Plates were read at 450 nm after stopping the color reaction with 2 N HCl. HSVgD2 in microsphere release samples were quantitated against standards using a four parameter log-logit curve fitting function.
33. Release supernatants were concentrated using a speed-vac, then diluted with PBS to approximate equivalent protein concentration (based on BCA) such that samples were loaded on SDS-PAGE gels at 1 μg/lane. Concentrated samples prepared in standard Laemmli buffer with and without b-mercaptoethanol then were loaded onto 4 to 20% Tris-glycine gels (Novex, 10 well x 1 mm gel thickness). Adjacent wells containing molecular weight markers and gD2 standards (1 μg/lane) were included for comparison. After developing and fixing, gels were silver-stained (Daiichi silver stain kit).
34. Samples were first centrifuged to remove particulate matter. Samples were then diluted to 100 μg/ml or less using PBS. Standards were prepared from gD2 bulk antigen by 1/2 serial dilutions in PBS resulting in gD2 concentrations from 100 μg/ml to 3.13 μg/ml in. The column used was an analytical C4 reverse phase column (Vydac 214TP5415) eluted under gradient conditions from 100% solvent A (0.1 % (w/v) trifluoroacetic acid (TFA), 10%(v/v)acetonitrile (ACN) to 100% solvent B (0.1% TFA, 90% ACN) linearly over 30 min using a flow rate of 0.5 ml/min. The injection volume was 100 μl and detection was carried out at 215 nm.
35. OTT G., BARCHFELD G.L., CHERNOFF D., RADHAKRISHNAN R., HOOGEVEST P.V. and VAN NEST G. - Design and evaluation of a safe and potent adjuvant for human vaccines. - In: Vaccine Design: The Subunit and Adjuvant Approach, J. M. Newman and M.F. Powell Eds., Plenum Press, New York, 1995, pp. 277-295.
36. Selected serum samples were measured for HSV-2 neutralizing titer using a serial dilution plaque reduction assay. The reported titer represents the reciprocal dilution required to reduce by half the cytolysis of confluent African green monkey kidney cells (Vero cells) by HSV-2 virus.
37. ELISA plates (Dynatech Lab. Microlite 2) were coated with gD2 antigen. After blocking (5% goat serum, 25 mM tris base, pH 7.5, 10 mM EGTA, 150 mM KCI, 2 mg/ml BSA, 0.5% Tween 20) and washing (20 mM Tris, pH 7.0, 5 mM EGTA, 150 mM NaCl, 0.5% Tween 20), wells were coated with 1/3 serially diluted serum samples or fecal extract samples. Fecal extract were assayed undiluted. Serum samples were first diluted 1/200 to 1/ 1000 using blocking buffer. A serum standard was included on each plate for quantitation purposes. Plates developed using Goat anti-mouse IgA or IgG biotin conjugate (EY Lab.; diluted 1/1000 in blocking buffer) followed by streptavidin-jellyfish aequorin conjugate (SeaLite Sciences, Inc.; diluted 1/500 in wash buffer without goat serum). Flash chemiluminescent reaction triggered using 10 mM calcium acetate in 50 mM Tris, pH 7.5 and measured using a luminometer (Dynatech Lab., model ML3000). The IgA results were corrected for IgG cross-reactivity.
38. Female Balb/C mice (n = 8) were immunized intramuscularly by two administrations, one month apart, of 10 μg doses of either gD2 alone or in combination with the adjuvant MF59. Serum IgG levels two weeks after the second administration showed a 120-fold increase in titer of the adjuvanted group above that of the unadjuvanted group.
39. UGGOZOLI M., O'HAGAN D.T. and OTT G.S. - Intranasal immunization of mice with herpes simplex virus (HSV) type II recombinant gD2: the effect of adjuvants on mucosal and serum antibody responces. - Submitted.