Search PubMed⌕ Search

Biomedical subjects

A M Prince

Publications and source records attributed to A M Prince.

At least 163 records · Page 9Linked to original sources
PubMed1983

A new hepatitis B vaccine containing HBeAg in addition to HBsAg.

A new vaccine is reported which contains HBeAg in addition to highly purified HBsAg. The rationale for this approach depends on the following data indicating that anti-HBe/anti-HBc may play an active role in prevention of HBV infection; (1) active immunization of chimpanzees with HBeAg(s) devoid of detectable HBsAg protected against subsequent challenge with HBV; (2) passive immunization of chimpanzees with an anti-HBe/anti-HBc intravenous immunoglobulin devoid of anti-HBs significantly delayed and appeared to attenuate HBV infection following subsequent challenge with HBV. The purification procedure utilized for production of the NYBC vaccine was designed to accomplish a high degree of purification with minimal use of complex equipment. This may facilitate eventual utilization of the vaccine on a mass scale for prevention of the HBV carrier state in high prevalence regions of the world. This procedure uses PEG precipitations and hydroxylapatite adsorption steps, followed by only a single isopycnic separation in a zonal rotor, to achieve a vaccine which is substantially free of serum proteins and detectable HBV DNA yet contains immunogenic quantities of HBsAg and HBeAg. The vaccine is inactivated by Tween 80 and formalin. Four lots have passed chimpanzee safety tests; two of them have been tested in clinical trials.

Animals↗
PubMed1983

Immunogenicity of HBeAg in the New York Blood Center hepatitis B vaccine.

A new hepatitis B vaccine has been developed which contains both HBsAg and HBeAg since evidence suggests that anti-HBe may have useful biologic activities. It was thus important to determine whether HBeAg is immunogenic in this type of a preparation. We now report data indicating that highly purified HBsAg particles, derived from HBeAg containing plasma, release a proportion of their contained cryptic HBeAg following the detergent treatment used in the preparation of this vaccine. Both the soluble and the residual particle associated HBeAg are immunogenic in guinea pigs. There was no detectable anti-HBe response in animals injected with similar HBsAg particles which had not been exposed to detergent.

Animals↗
PubMed1983

Hepatitis B vaccine: safety study in anti-HBs seropositive human volunteers.

HBsAg, which has been purified from HBsAg and HBeAg positive plasma, was repeatedly applied to human volunteers, who were seropositive for anti-HBs. The intramuscular or subcutaneous injections caused a clear booster effect on anti-HBs concentrations in serum. The injections were well tolerated. Only minor local side effects occurred. Vaccination left serum transaminase activities unaffected. None of the volunteers developed serologic or clinical signs related to viral hepatitis.

Adult↗
PubMed1983

Hepatitis B vaccine: safety study in anti-HBs seronegative human volunteers.

A hepatitis B vaccine which has been prepared from HBsAg and HBeAg positive human plasma and which consists of purified HBsAg in an alum suspension was investigated for safety and immunogenicity in a clinical trial. Twenty-three anti-HBs seronegative volunteers received three injections each of 40 micrograms HBsAg intramuscularly. No rise in serum transaminase activities occurred during the follow-up period, and none of the volunteers developed clinical signs related to viral hepatitis. Only minor side reactions like burning or reddening at the site of injection were reported by the volunteers. 100% seroconversion occurred within 150 days after first vaccination. The subsequent two vaccinations caused a strong booster effect.

Adult↗
PubMed1983

Specificity and significance of hepatocellular ultrastructural changes in non-A, non-B hepatitis in chimpanzees.

324 liver biopsies from 71 chimpanzees with and without non-A, non-B (NANB) hepatitis have been examined by electron microscopy (E.M.) for hepatocellular changes reported to be associated with this disease. At least 2 types of ultrastructural cytoplasmic alterations were found in each of 23 cases of acute and 6 cases of chronic NANB hepatitis. Nuclear modifications were never seen. Similar ultrastructural alterations were found in infections derived from 9 different human blood borne NANB cases. In 9 animals which had received 5 different inocula, Pfeifer Type I, II, III and IV changes were seen; 3 of the 4 types occurred in 10 animals and 2 of the types in 5 animals. Type II and III changes were almost always seen together. All 4 types of alteration were usually found in biopsies taken near the peak of ALT elevation. Five of 6 animals in whom E.M. changes were detected in serial samples over a 1 1/2 to 4 1/2 year period had concurrent chronic ALT abnormality. Two of these 6 animals did not develop ALT abnormality until years after the original acute episode though E.M. changes were detected throughout this period. There was generally a good correlation between onset and duration of ALT abnormality and period when E.M. changes were detected. All samples from animals not exposed to NANB virus(es) were negative by E.M. Our findings indicate the ultrastructural cytoplasmic alterations to be highly specific for NANB infection. Since each of the 9 isolates produced essentially the same pattern of E.M. changes, it is likely that a single NANB hepatitis virus group accounts for most blood borne NANB hepatitis.

Alanine Transaminase↗
PubMed1983

Factor VIII concentrate from cold sterilized human plasma.

beta-Propiolactone (beta-PL) in combination with UV irradiation (UV) is an established method for the sterilization of factor IX concentrate or stabilized human serum. Because of the extreme sensitivity of factor VIII to beta-PL, the standard beta-PL/UV procedure cannot be used to obtain hepatitis-safe factor VIII concentrate. It has been shown in chimpanzees that from a cryoprecipitate containing hepatitis non-A, non-B viruses in addition to hepatitis B viruses a factor VIII concentrate (160 U/10 ml) can be prepared by a modified beta-PL/UV procedure, which induces neither hepatitis B nor hepatitis non-A, non-B in experimental animals; the non-sterilized original cryoprecipitate proved to be infectious.

Animals↗
PubMed1982

[Hepatitis B vaccine. Assessment of vaccines obtained from human plasma].

This review addresses three questions: Why should HBV vaccines be used? Who should receive them? How should they be made and given? It is suggested that the major function of HBV vaccine, in addition to preventing acute hepatitis in high-risk groups, is prevention of chronic HBV infections (i.e., the HBV carrier state) particularly in high-prevalence regions, with their attendant eventual morbidity and mortality due to cirrhosis and hepatocellular carcinoma. Target populations for vaccine use, subject to vaccine availability, are defined in accordance with this concept. Existing approaches to vaccine manufacture are compared and discussed; all appear to provide safe and immunogenic vaccines. However, it is too early to draw conclusions as to their relative immunogenicity, efficacy, and economy.

Hepatitis B↗
PubMed1982

Hepatitis B virus vaccine: identification of HBsAg/a and HBsAg/d but not HBsAg/y subtype antigenic determinants on a synthetic immunogenic peptide.

On the basis of theoretical considerations, a peptide (H peptide) was synthesized by Hopp and Woods [Hopp, T. P. & Woods, K. R. (1981) Proc. Natl. Acad. Sci. USA 78, 3824---3828]. This peptide contains a sequence of six amino acids postulated to represent the major epitope, or antibody-combining site, of hepatitis B virus surface antigen (HBsAg). We have used passive hemagglutination inhibition with monospecific antibodies against the a, d, and y subdeterminants of this antigen and against human serum albumin to investigate the antigenic specificities on this peptide, and we have found it to contain the HBsAg/a and HBsAg/d but not HBsAg/y or human serum albumin subdeterminants. When the peptide was conjugated onto human erythrocytes and injected into mice, it induced the formation of anti-HBsAg with and without the use of Freund's adjuvant. If anti-HBsAg/a confers immunity to infection with hepatitis B virus, as is generally thought, these findings may permit the development of a synthetic vaccine lacking all unnecessary antigenic determinants.

Amino Acid Sequence↗
PubMed1981

Long-term tolerance and recovery of beta-propiolactone/ultraviolet (beta PL/UV) treated PPSB in chimpanzees.

Recent experiments have shown that a preparation of PPSB (factor IX concentrate) derived form beta PL/UV treated plasma was not infectious in chimpanzees with respect to hepatitis B and non-A, non-B. To answer the question whether the beta PL/UV treatment influences the tolerance and efficacy of the PPSB-concentrate, long-term application of PPSB-Biotest was carried out in chimpanzees. After 10 applications of 25 U factor IX/kg at weekly intervals, no signs of intolerance were observed by measurement of blood pressure during i.v. application and by means of skin-testing. Determination of coagulation factor activity during the application period revealed the same factor IX recovery at the beginning and at the end of the study.

Animals↗
PubMed1981

Effect of combined treatment of serum containing hepatitis B virus with beta-propiolactone and ultraviolet irradiation.

The effect of cold sterilization by beta-propiolactone (beta-PL) and ultraviolet (UV) irradiation of serum contaminated with infectious hepatitis B virus (HBV) was investigated in chimpanzee. Chimpanzees given 0.1 ml/kg of the undiluted HBV serum estimated to contain 10(7)-10(8) CID50/ml developed acute hepatitis B infection 4 weeks after inoculation. Chimpanzees injected with the same undiluted hepatitis serum treated with beta-PL/UV developed hepatitis B infection 14 weeks later. Based on the published linear relationship between log dose of HBV and incubation period in chimpanzees this indicates a 10(6)-fold reduction in infectivity titer. Animals inoculated with the serum diluted 1:1,000 showed manifest hepatitis B infection 11 weeks later. Animals inoculated with serum diluted 1:1,000 and then cold sterilized with beta-PL/UV showed no signs of hepatitis B infection. Sensitive proteins are not denatured by beta-PL/UV cold sterilization.

Animals↗
PubMed1981

Epidemiology of hepatitis B infection in Liberian infants.

To provide background for a hepatitis B vaccine efficacy trial, sera were collected from 0- to 4-year-old Liberian infants and their mothers, on two occasions an average of 14.75 months apart, and tested for serological markers of hepatitis B virus infection. The prevalence of the hepatitis B surface antigen (HBsAg) was 2.9% in the 0- to 6-month age group and 23% in infants 3 to 4 years of age. HBsAg persisted for the 14.75-month average follow-up period in 80.8% of the infants tested. The annual incidence of development of HBsAg was 18.9% for infants less than 1 year of age and 13.6% in infants 3 to 4 years of age. Infants born to HBsAg carrier mothers had significantly higher age-specific prevalence and incidence of hepatitis B virus infection. However, it was estimated that only a minor proportion of hepatitis B infections in Liberia are derived by vertical transmission from carrier mothers.

Adolescent↗
PubMed1980

Evaluation of the effect of betapropiolactone/ultraviolet irradiation (BPL/UV) treatment of source plasma on hepatitis transmission by factor IX complex in chimpanzees.

To evaluate the safety of a beta-Propiolactone/Ultraviolet (BPL/UV), irradiated Factor IX complex preparation we inoculated 8 chimpanzees with 25 units Factor IX/Kilo from a pool of 5 production lots which had been treated in this manner. These lots were derived from approximately 1,000 donors. Animals were followed with weekly tests for hepatitis B serologic markers and transaminases, and biweekly liver biopsies, for 6 months. No evidence of transmission of hepatitis B, or non-A, non-B viruses was observed. To further evaluate the BPL/UV procedure a plasma pool was intentionally contaminated with hepatitis B virus and one half of the pool treated with BPL/UV. Factor IX complex was isolated from the treated and untreated pools and each was inoculated into 4 chimpanzees. The Factor IX derived from untreated plasma infected all four animals with an average incubation period of 10.5 weeks, whereas that prepared from PBL/UV treated plasma infected only one of four animals with an incubation period of 21 weeks. These results were interpreted as suggesting that BPL/UV can inactivate approximately 99.9% of hepatitis B virus infectivity.

Animals↗