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C O Tacket

Publications and source records attributed to C O Tacket.

33 records · Page 2Linked to original sources
PubMed1990

Safety, immunogenicity, and efficacy against cholera challenge in humans of a typhoid-cholera hybrid vaccine derived from Salmonella typhi Ty21a.

A live oral vaccine consisting of attenuated Salmonella typhi Ty21a expressing Vibrio cholerae O1 Inaba lipopolysaccharide (LPS) O antigen was constructed and tested in volunteers for safety, immunogenicity, and efficacy. Fourteen adults ingested three doses of 10(10) viable organisms with buffer. One month later, 8 vaccinees and 13 unimmunized controls were challenged with 10(6) pathogenic V. cholerae O1 E1 T or Inaba organisms. No significant adverse reactions to vaccination were observed. All volunteers had significant rises in serum immunoglobulin G (IgG) antibody to S. typhi LPS. Only 2 (14%) of 14 had significant rises in serum IgA or IgG antibody to Inaba LPS, and 5 (36%) of 14 had fourfold rises in vibriocidal antibody. In the challenge study, diarrhea occurred in 13 of 13 controls and 6 of 8 vaccinees (vaccine efficacy, 25%; P = 0.13). The vaccine significantly reduced the severity of the clinical illness (P less than 0.05) and caused decreased excretion of challenge vibrios (P less than 0.05). Although the typhoid-cholera hybrid vaccine did not provide significant protection overall against experimental cholera, this study demonstrates the importance of antibody to V. cholerae O antigen in ameliorating clinical illness and illustrates the use of an S. typhi carrier vaccine strain expressing a foreign antigen.

Antibodies, Bacterial↗
PubMed1990

Adjuvants.

In summary, HIV vaccine studies described have generally not been designed to measure the effect of the adjuvant or to make comparisons between adjuvants. In only one study was a head-to-head comparison made between HIV antigen alone and antigen formulated with different adjuvants. We hope that future experiments with HIV/SIV vaccine candidates will be designed to determine the relative potency and safety of different adjuvants. Unfortunately, such experiments tend to be tedious and expensive. The design of these studies will need to address a number of variables which influence the response to the vaccine, including route and schedule of immunization, genotype and species of the vaccinated subject, and intrinsic characteristics of the antigen. In addition, the immunologic endpoints should include measurement of both B and T cell function. The carrier/adjuvant/antigen formulation should be hand-tailored and then standardized so that it is manufactured reproducibly without producing different biological effects between lots, and the vaccine formulation should be stable on storage and shipping. Finally, we obviously need to identify and test the protective antigen or antigens. The best adjuvant will never correct the choice of the wrong epitope.

AIDS Vaccines↗
PubMed1990

Salivary antibodies to human immunodeficiency virus type 1 in a phase I AIDS vaccine trial.

HIV-1-specific secretory antibodies may be a desirable outcome in individuals receiving AIDS vaccines. We investigated parotid and whole saliva samples for HIV-specific antibodies collected from five volunteers who received a recombinant HIV-1 envelope glycoprotein (rgp160) vaccine. Ten healthy, adult volunteers received intramuscularly either three doses of rgp160 (40 or 80 micrograms), a hepatitis B vaccine, or a placebo on days 0, 30, and 180. Saliva samples were collected on days 0, 28, 60, 120, 194, and 270 from the volunteers. All volunteers were negative for serum HIV antibodies by ELISA (Abbott). By Western blotting, serum antibodies to envelope antigens were demonstrated in one of three individuals who received the low dose vaccine and two of two who received the high dose. Antibodies to gp160 were detected in whole saliva on day 194 from one of these individuals by Western blotting. Parotid saliva collected on all dates did not contain detectable HIV-specific antibodies. The finding of HIV-1-specific antibodies in whole saliva following vaccination may indicate that development of mucosal immunity is possible.

Blotting, Western↗
PubMed1988

Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR.

The genes encoding the A (toxic) subunit of cholera toxin were deleted from pathogenic Vibrio cholerae O1 strain 569B by recombinant techniques, leaving intact production of immunogenic, non-toxic B subunit. The resultant strain, CVD 103, evaluated for safety, immunogenicity, and efficacy as a live oral vaccine, was highly attenuated and elicited strong antibacterial and antitoxic immune responses; a single dose significantly protected volunteers against challenge with pathogenic V cholerae O1 of either serotype or biotype. A further derivative, CVD 103-HgR, which has an Hg++-resistance gene to differentiate it from wild-type vibrios, was also well-tolerated, immunogenic, and protective; moreover, faecal excretion of this derivative was significantly lower than that of CVD 103, which should minimise environmental spread of the vaccine. CVD 103-HgR is a candidate for expanded clinical trials in endemic areas.

Administration, Oral↗
PubMed1988

Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli is a common cause of traveler's diarrhea. Prophylaxis against traveler's diarrhea has been associated with side effects from bismuth subsalicylate and the development of resistance to antimicrobial agents. We undertook a double-blind controlled trial in which a bovine milk immunoglobulin concentrate with high titers of antibodies against enterotoxigenic E. coli was used as prophylaxis against E. coli challenge in volunteers. Lyophilized milk immunoglobulins were prepared from the colostrum of cows immunized with several enterotoxigenic E. coli serotypes and fimbria types, E. coli heat-labile enterotoxin, and cholera toxin. As a control, an immunoglobulin concentrate with no anti-E. coli activity was prepared. Ten volunteers received buffered immunoglobulin concentrate against enterotoxigenic E. coli, and 10 received the control immunoglobulin concentrate, dissolved in water, three times a day. No side effects were observed. On the third day of immunoglobulin prophylaxis, the volunteers were given 10(9) colony-forming units of enterotoxigenic E. coli H10407 (O78:H11). This strain produces colonization factor antigen I and heat-labile and heat-stable enterotoxins. None of the 10 volunteers receiving the immunoglobulin concentrate against E. coli had diarrhea, but 9 of the 10 controls did (P less than 0.0001). All volunteers excreted E. coli H10407. We conclude from these preliminary results that milk immunoglobulin concentrate may be an effective prophylaxis against traveler's diarrhea.

Adult↗
PubMed1988

Persistence of antibody titres three years after vaccination with Vi polysaccharide vaccine against typhoid fever.

After a single injection of purified Vi polysaccharide vaccine against typhoid fever, serum titres were followed in student volunteers by passive haemagglutination assay and by radioimmunoassay. Elevated Vi antibody titres were still present after 36 months. This preliminary study should be followed by further investigations on the extent and duration of protection provided by Vi vaccine, and on volunteers in endemic areas.

Adult↗
PubMed1988

The current status of typhoid vaccine development and clinical trials with typhoid vaccines.

The killed whole cell typhoid vaccines, although protective, have limited usefulness because of the adverse reactions they evoke. In contrast, new typhoid vaccines protect without reactogenicity. Attenuated oral vaccine Ty2la has been evaluated in field trials of efficacy in Santiago, Chile. Three doses of Ty2la in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Ty2la has reached the stage of being a practical public health tool. Two double auxotrophic (Aro-, Pur-) mutant strains of S. typhi (541Ty and 543Ty) were well-tolerated and stimulated cell-mediated immune responses but evoked little serological response. Parenteral purified Vi polysaccharide of S. typhi (single 25 mcg dose) was safe and immunogenic and provided 64-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.

Adult↗
PubMed1987

A plasmid of enterohemorrhagic Escherichia coli O157:H7 is required for expression of a new fimbrial antigen and for adhesion to epithelial cells.

Of 14 strains of Escherichia coli O157:H7 isolated from patients with hemorrhagic colitis or hemolytic uremic syndrome that were examined for fimbriae, the presence of plasmids, and the ability to adhere to intestinal cells, 13 possessed a 60-megadalton plasmid and were fimbriated as assessed by electron microscopy. These strains adhered to Henle 407 intestinal cells but not to HEp-2 cells or erythrocytes. Three strains were cured of the plasmid and thereafter failed to express fimbriae and lost the ability to adhere to intestinal cells. Conversely, E. coli K-12 transformed with the 60-megadalton plasmid from each of the three strains produced fimbriae and was able to adhere to intestinal cells. A single fimbrial subunit of 16 kilodaltons was observed when purified fimbriae from the transformants and from the 60-megadalton plasmid-containing E. coli O157:H7 strains were disaggregated and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera raised against one preparation of the purified fimbriae reacted strongly with 12 of 14 O157:H7 isolates in an agglutination assay and with purified fimbrial preparations from five E. coli O157:H7 strains in an enzyme-linked immunosorbent assay.

Animals↗
PubMed1987

Purification, morphology, and genetics of a new fimbrial putative colonization factor of enterotoxigenic Escherichia coli O159:H4.

The ability to colonize the small intestine is essential for the pathogenesis of diarrhea caused by enterotoxigenic Escherichia coli (ETEC). Colonization is mediated by fimbriae (pili), of which there are several antigenically distinct types, including colonization factor antigen I, colonization factor antigen II (CS1, CS2, and CS3), and PCF8775 (CS4, CS5, and CS6). These fimbriae are associated with certain ETEC O serogroups. Serogroup O159 has had no known colonization factor. We found a distinct plasmid-encoded fimbria composed of 19-kilodalton protein subunits associated with ETEC serotype O159:H4. Rabbit antibody against this purified fimbria reacted with a single 19-kilodalton protein band as seen by Western immunoblot of sheared-cell preparations. The rabbit antibody, treated with colloidal-gold-labeled goat anti-rabbit immunoglobulin G, bound specifically to fimbriae when cells were examined with an electron microscope. Of 10 available ETEC O159:H4 strains from Europe, Bangladesh, and Kenya, 6 expressed this type of fimbria; its true prevalence among ETEC strains is unknown. This putative colonization factor of O159:H4 joins other ETEC fimbriae as potentially useful immunogens against human diarrhea.

Antigens, Bacterial↗
PubMed1985

An outbreak of multiple-drug-resistant Salmonella enteritis from raw milk.

In early 1983, an outbreak of illness caused by raw milk contaminated with multiple-antimicrobial-resistant Salmonella typhimurium occurred in Arizona. One of the cases involved a 72-year-old woman who died with Salmonella enteritis and sepsis that had not responded to treatment with chloramphenicol. The S typhimurium isolates from this patient, from other ill persons, and from raw milk were resistant to ampicillin, chloramphenicol, kanamycin sulfate, streptomycin, sulfonamide, and tetracycline. These resistances were mediated by a 105-megadalton R plasmid. During the epidemic period, 43% of the S typhimurium isolates submitted to the Arizona Department of Health Services were resistant to chloramphenicol, and 80% of these possessed the same plasmid resistance. Although there was evidence of spread of the S typhimurium in the community, there was no evidence of spread of this Salmonella R plasmid to the normal flora of patients or their family members a median of 14 weeks after the infection. This outbreak demonstrates the ability of drug-resistant Salmonella to spread from the animal to the human reservoir and, in a suitable host, produce a fatal infection.

Aged↗
PubMed1985

An outbreak of Yersinia enterocolitica infections caused by contaminated tofu (soybean curd).

The authors investigated 50 Yersinia enterocolitica infections during an outbreak of illness due to contaminated tofu (soybean curd) in Washington State between December 15, 1981 and February 22, 1982. The most common clinical syndrome (36 patients) was gastrointestinal infection for which two patients underwent appendectomies and one a partial colectomy. Of the remaining 14 patients, six had extraintestinal infections, two had fever alone, and six were asymptomatic. The patients with enteric infections were younger (median age three years) than those with extraintestinal infections (median age 28 years). In a case-control study of enteritis patients, illness was associated with ingestion of one brand of tofu (p less than 0.01). Ninety-two per cent of patients with gastrointestinal infections and 33% with extraintestinal infections recalled having eaten the implicated product. Y. enterocolitica serotype O:8, the most common serotype isolated from patients, was also isolated from tofu and the plant's untreated spring water. There was little clinical or laboratory evidence of secondary spread to family members who did not eat tofu. The outbreak demonstrates the transmission of Y. enterocolitica from nature to man and the potential of "natural" foods as vehicles for environmental pathogens.

Adolescent↗
PubMedDate not supplied

Progress in vaccines against typhoid fever.

The widely available heat-phenol-inactivated whole cell typhoid vaccine, which provides approximately 65% protection, has limited usefulness because of the adverse reactions it evokes. In contrast, several new typhoid vaccines promise protection without reactogenicity. Attenuated oral vaccine Ty21a has been evaluated in three field trials of efficacy in Santiago, Chile, involving 530,000 schoolchildren. Three doses of Ty21a in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Fewer doses conferred less protection, while adding a fourth dose significantly enhanced protection; increasing the interval between doses did not improve protection. Large-scale vaccination with Ty21a appeared to cause a herd-immunity effect. Ty21a has reached the stage of being a practical tool for public health. With respect to other vaccines, the safety and immunogenicity of an auxotrophic (Aro-,Pur-) Salmonella typhi mutant (strain 541Ty) has recently been evaluated. Lastly, parenteral purified Vi polysaccharide of S. typhi was safe and immunogenic and provided 64%-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.

Chile↗
PubMedDate not supplied

A voluntary serosurvey and behavioral risk assessment for human immunodeficiency virus infection among college students.

The authors conducted a voluntary serosurvey and educational campaign among 3394 undergraduate students attending the University of Maryland at College Park to determine the prevalence of and risk factors for human immunodeficiency virus type 1 (HIV-1) infection. Two students were seropositive (0.06%, 95% confidence interval 0-0.15%). Both were homosexual men with multiple sexual partners. Despite the low prevalence of infection, potential risk factors for transmission of HIV-1 were common, as assessed by a self-administered anonymous questionnaire. These included a previous sexually transmitted disease (12.6%), male homosexual intercourse (4.8% of men), heterosexual anal intercourse (25.3%), heterosexual intercourse with a person at risk (an HIV-1 infected person, a bisexual man, a parenteral drug user, a female prostitute, or a hemophiliac) (5.2%), multiple sexual partners (21% reported 10 or more lifetime partners), and intravenous drug use (1.3%). Assessment of the efficacy of our program by comparing responses on pre- and post-test questionnaires showed gains in knowledge about heterosexual transmission of HIV-1 and an increase in the reported frequency of condom use 1-2 months after participating in the survey. The authors conclude that HIV-1 infections are occurring among college students but in our study group remain confined to persons with known high-risk behavior; however, practices that may support transmission are common, and programs designed to diminish these behaviors among college students are needed.

Adolescent↗