Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.     

Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new, highly purified, heat-treated equine rabies immunoglobulin, administered either alone or in association with a purified, Vero-cell rabies vaccine

A clinical evaluation of a new, purified, heat-treated equine rabies immunoglobulin (PHT-Erig), F(ab')2 preparation, was carried out in Thailand and in the Philippines-two countries where rabies is endemic. An initial prospective, randomised, controlled trial (Study 1), compared the safety and pharmacokinetics (serum concentrations of rabies antibodies) after administration either of PHT-Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A second trial (Study 2) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV), administered in association with either Erig PMC or PHT-Erig. In Study 1, 27 healthy, Thai adults received a 40 IU kg(-1) dose of either Erig PMC (n = 12) or PHT-Erig (n = 15) via the intramuscular (i.m.) route; half of the dose was injected into the deltoid area and the other half into the buttocks. Serum for rabies antibody determination and F(ab')2 concentration was collected at hours (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were safe, with no serious adverse events, and in particular, no anaphylactic reactions or serum sickness was reported. A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products. Nonetheless, the relative bioavailability of 93% and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar. The antibody level in either group were low throughout the 15-day study period. The geometric mean titer (GMT) values ranged from group 0.027-0.117 IU ml(-1) in the Erig group and from 0.029 to 0.072 IU ml(-1) in the PHT-Erig. There was no significant difference between the evolution of GMT values for the two groups. In Study 2, 71 healthy volunteers received 40 IU kg(-1) via the intramuscular route of either Erig PMC (n = 36) or PHT-Erig (n = 35) on D0, in association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and D28. No serious reactions were reported in either group. In particular, no immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were observed. Over the 28-day follow-up period, GMT profiles of the two groups were statistically equivalent. On D14, 100% of the subjects had protective antibody titers (anti-rabies antibodies > or = 0.5 IU ml(-1), which is the WHO-recommended level of seroconversion), and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen. On D28, the GMT values were 33.2 IU ml(-1) (95% CI, 23.8-46.1 IU ml(-1)) in the Erig PMC/PVRV group and 31.4 IU ml(-1) (95% confidence interval, CI, 23.4-42.2 IU ml(-1)) in the PHT-Erig/PVRV group, showing evidence of adequate vaccine-induced antibody responses in both groups. The increased purity, the heat-treatment step introduced in the manufacturing process of PHT-Erig, and the good clinical results substantiate the use of this new generation, purified equine F(ab')2 preparation in the post-exposure prophylaxis of rabies.     

Postinfectious antirabic vaccination of children with duck embryo vaccine and heterologous rabies hyperimmunity serum (author's transl)

After contact with a rabies-infected rabbit, 31 Persons were submitted to complete vaccination treatment with duck embryo vaccine, comprising of injections of 1.0 ml each every fast night and two booster injections of 1.0 ml each, which were administered 10 and 20 days, respectively, after the end of the 14 days' vaccination series. After performance of intracutaneous and ophthalmic tests, 18 children received heterologous rabies immunserum (Behring) in a dose of 0.2 ml per kg of body weight before the beginning of the vaccination series. Six weeks after the start of the vaccination series neutralizing and complement-fixing antibodies (rate of conversion 100 per cent) were detected in all patients. The mean titre of neutralizing antibodies (mouse test 200 LD 50 Fixed virus, strain CVS) amounted to 1:140, that of complement-fixing antibodies to 1:41. Severe incompatibility reactions were not observed. Outpatient treatment with duck embryo vaccine therefore seems to be fully justified.     

Immunization of cows with ferric enterobactin receptor from coliform bacteria

The serum and milk immunoglobulin (Ig) G responses of lactating dairy cows were determined following immunization with ferric enterobactin receptor FepA. Escherichia coli 471 was cultured in iron-depleted medium, and outer membrane proteins were extracted by 2% N-lauroylsarcosine sodium salt and 2% Triton X-100. The FepA was isolated from the outer membrane proteins by ion-exchange chromatography. Twenty cows were assigned to four treatment groups of 5 cows blocked by breed and days in milk. Treatment groups were vaccinated with 100 micrograms of FepA, 500 micrograms of FepA, Escherichia coli J5 bacterin, or sterile phosphate-buffered saline. Primary immunization was at approximately 200 d in milk, and booster immunizations were given 14 and 28 d later. Serum and whey IgG titers to FepA in cows vaccinated with FepA were significantly higher than those from cows vaccinated with either E. coli J5 bacterin or phosphate-buffered saline. Serum and whey IgG titers to FepA were elevated by 14 d in cows vaccinated with FepA. Significant differences were not observed between doses of FepA. The degree of cross-reactivity of purified IgG from cows vaccinated with FepA to E. coli and Klebsiella pneumoniae isolates was significantly higher than that to a control isolate that lacked FepA production. Immunization with FepA elicited an immunological response in serum and milk.     

Problems associated with rabies preexposure prophylaxis

With the rabies vaccine presently available for preexposure prophylaxis, 20% of all individuals do not have seroconversion following routine immunizations, and 5% are allergic to this vaccine. Two experimental rabies vaccines of cell culture origin offering greater purity and potency were evaluated by means of a double-blind experiment. Thirty-one volunteers who did not have seroconversion or who were allergic to duck embryo rabies vaccine received rabies vaccine produced in either human diploid cell culture (WI-38), or hamster kidney-cell culture. All volunteers had seroconversion within 14 days of receiving a single injection of other experimental vaccine. Clinical side effects were only minor.     

Comparative study of 2 variants of a modified esophageal transection in the Sugiura-Futagawa operation

From December of 1990 to December of 1997, 119 subjects visited to our hospital to receive post-exposure therapy using purified chick embryo cell rabies vaccine manufactured by the Chem-Sero-Theraptic Institute (Katestuken), because they had been bitten by supposed rabid animals abroad. The forty of the subjects (male: 25, female: 15) wished to have their anti-rabies antibody levels examined. The number of samples taken after 5 or 6 shots rabies vaccine were 30 and 15, respectively. The antibody levels after 6 shots of rabies vaccine varied from 1.0 IU/ml to 10.1 IU/ml. After 5 shots the antibody levels fluctuated from under 0.1 IU/ml to over 8.8 IU/ml, and 3 subjects were found to have antibody titers of under 0.5 IU/ml which is the WHO minimal protective level. Two of these 3 subjects found to have antibodies of 1.0 IU/ml and 3.1 IU/ml. after the 6th injection. However, these 3 subjects had the hazard to have rabies despite post-exposure immunization, because the incubation period of rabies is found to be 1-3 months in about 60% of the cases. The potency of Kaketsuken's rabies vaccine should be increased to provide higher antibody levels.     

Adverse reactions after diphtheria-tetanus booster in 10-year-old schoolchildren in relation to the type of vaccine given for the primary vaccination

This prospective open study investigated adverse reactions in 527 schoolchildren to a diphtheria-tetanus (DT) booster given within a national vaccination programme at 10 years of age. Evaluation was based on those whose immunization records showed that they had received either three doses of an adsorbed DT vaccine (n = 388) or a non-adsorbed DT-pertussis vaccine (DTP) (n = 69) for primary series vaccination. No differences in systemic reactions to the booster between the two groups were observed. Local reactions were significantly (p < 0.001) more common 1 day after vaccination in children who had received DT for primary series vaccination: redness, 73% compared with 23%; swelling, 56% versus 15%; and itching, 47% versus 21%. One and 2 weeks after the booster, itching was still more pronounced in the group who had received DT for primary series vaccination (p < 0.001 and 0.014, respectively). The study indicates that there was a real basis for the increase in spontaneous notifications of local side-effects to the school DT booster in Sweden. The most likely cause for the increase seems to be the aluminium adjuvant in the vaccine given for primary vaccination, a late and unexpected consequence of a change in the infant immunization programme.     

Serologic response to revaccination with two rubella vaccines

Three years after receiving rubella vaccine, 1,060 elementary school children living on the island of Maui, Hawaii, were revaccinated with either HPV-77 DE-5 or RA 27/3 rubella vaccine given subcutaneously or intranasally in order to compare the effectiveness of these two vaccines in raising antibody titers. RA 27/3 was the more effective booster vaccine, producing fourfold or greater titer rises in 20.1% of recipients, including 80% of children with hemagglutination-inhibiting antibody titers less than or equal to 1:40 at the time of revaccination, intranasal revaccination was not significantly more effective than subcutaneous revaccination, although it did elicit higher titers in children who responded. Responses differed according to the vaccine that children had received three years earlier. Because antibody titers have persisted in vaccinated children, routine administration of a second dose of rubella vaccine is not currently recommended.     

Failure of protection induced by a Brazilian vaccine against Brazilian wild rabies viruses

This report shows that the SMB vaccine currently used in Brazil for human immunisation provides different degrees of protection in mice, depending on the rabies virus strain used as challenge. Using the NIH and Habel potency tests to evaluate the protective activity of rabies vaccine, we observed that vaccinated mice showed a higher resistance to a challenge with a fixed rabies virus (CVS-Challenge Virus Strain). The vaccine potency using the Habel or NIH tests was respectively > 6.4 (log 10) and 1.0 (Relative Potency-RP) when the fixed rabies virus was used for challenge, and from 2.9 to 4.3 (log 10) or 0.13 to 0.8 (RP) when different wild rabies viruses were used for challenge. The presence of virus neutralising antibodies (VNA) could not explain the differences of susceptibility after vaccination, since sera of vaccinated animals had similar VNA levels against both fixed and wild strains before virus challenge (respectively, 5.6 +/- 0.24 and 5.0 +/- 0.25 IU/ml of VNA against the fixed rabies virus and the 566-M strain of wild rabies virus in sera of mice vaccinated with 0.2 units of vaccine). Only cell-mediated immunity parameters correlated with the protection induced by vaccination. The IFN gamma titers found in sera and brain tissues of animals challenged with CVS strain were higher (from 36.7 +/- 5.7 to 293.3 +/- 46.2 IU/ml) than those found in mice challenged with 566-M virus strain (from 16.7 +/- 5.8 to 36.7 +/- 5.8). The proliferation index of spleen cells obtained with CVS stimulation reached a maximal value of 15.1 +/- 0.7 while spleen cells from vaccinated mice stimulated with 566-M virus failed to proliferate. The implications of these data in human protection by vaccination are discussed.     

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age

METHODS: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS: There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.     

Occlusion of the femoral artery induced fos-like immunoreactive neurons in the lateral habenular nucleus projecting to the midbrain periaqueductal gray in the rat

BACKGROUND: Inactivated hepatitis A vaccines are licensed with a vaccination schedule based on two injections of vaccine given at least 6 months apart. METHODS: Two vaccination schedules for the inactivated hepatitis A vaccine, AvaximTM (Pasteur Mérieux Connaught, Lyon, France), were compared in a monocentric, randomized, open trial. Two doses of the vaccine were given at intervals of either 6 months (0-6 month group) or 12 months (0-12 month group) to 96 adult volunteers. Anti-hepatitis A virus (HAV) antibody titers were determined in a blind fashion using the modified RIA (mRIA) HAVABtrade mark assay. After excluding subjects with positive preimmunization anti-HAV titers and those with protocol deviations, both groups were still comparable by sex ratio and mean age. RESULTS: Four weeks (28 6 4 days) after the first dose, the seroconversion (SC) rate of initially HAV-seronegative subjects (antibody titer < 20 mIU/mL) was 100% in the 0-6 month group and 96. 9% in the 0-12 month group, with corresponding geometric mean titer (GMT) values (95% CI) of 369 mIU/mL (274-497 mIU/mL) and 445 mIU/mL (292-679 mIU/mL), respectively. After 6 months, SC was obtained in all subjects, and the corresponding GMT values were 349 mIU/mL and 359 mIU/mL in the 0-6 month group and the 0-12 month group, respectively. Four weeks after the booster dose given at 6 months, a 14.5-fold rise in GMT was observed. In the 0-12 month group, anti-HAV GMT values decreased by only 20% from 6 months to 12 months with a pre-booster GMT value of 286 mIU/mL at the 12-month evaluation. Four weeks after the booster given at 12 months, a 22. 5-fold rise in GMT was observed. Statistical analysis showed that the two vaccination schedules were comparable in their ability to boost antibody titers. Unsolicited reactions to vaccination were not different to those reported during earlier trials. Less than 12% of the vaccinees reported reactions after the first dose (11/93), or after the booster dose (11/92). CONCLUSIONS: This trial demonstrated antibody persistence is excellent for at least 12 months after one dose of this vaccine, and that a booster may be given at any time between 6 and 12 months after primary immunization.     

Evaluation of Wistar RA27/3 rubella virus vaccine in children

Because the Wistar RA27/3 strain rubella virus vaccine has potentially important advantages over rubella vaccines currently licensed in the United States, a field trial was conducted in Minnesota and Wisconsin in 1974 to evaluate RA27/3 in this country. Two hundred eighty-five (99.7%) of 286 susceptible children given RA27/3 subcutaneously seroconverted, with a geometric mean hemagglutination inhibition (HI) titer of 81.2. Twenty-eight (23%) of 122 children with rubella antibodies before immunization had fourfold or greater rises in rubella HI titers. The highest percentage of booster responses occurred in children with low preimmunization titers. Side effects were reported in 34% of subjects, but only one reaction associated with RA27/3 was serious: in a 5-year-old boy, arthritis of the left hip developed 31 days after immunization. This study indicates that RA27/3 vaccine produced a very high rate of seroconversion with high postimmunization HI titers. The ability to elicit significant booster responses in children with low levels of HI antibodies suggests that RA27/3 could be used to boost immunity in women of childbearing age whose rubella titers have declined to undetectable levels.     

Effect of 2 urban emergency department immunization programs on childhood immunization rates

BACKGROUND: Emergency departments (EDs) are recommended as sites for immunizing children. However, there is little information about the effect of ED immunization programs on immunization rates. OBJECTIVES: To assess the ability of 2 ED immunization programs to vaccinate children and to measure the effect of the programs on immunization rates after the ED visit and 6 months later. DESIGN: A prospective cohort study. Emergency department patients were screened for immunization status, and vaccinations were offered to patients who either were documented to be eligible or were eligible by age and had no documented records. A systematic, sequential sample of those accepting vaccinations (study patients) was compared with a systematic, sequential sample of those not vaccinated (control subjects). Telephone interviews and medical record reviews were performed 6 months after the ED visit to verify dates of immunizations. Results were weighted to reflect the sampling frames of patients screened by the 2 programs. SETTING: Two EDs in New York City (in Manhattan and the Bronx) and the surrounding primary care offices. PATIENTS: Children (aged 0-6 years) screened for immunization status by the ED immunization program during a 10-week period; these included 210 children from the Manhattan ED (106 vaccinated in the ED) and 274 children from the Bronx ED (129 vaccinated in the ED). INTERVENTION: Emergency department immunizations. MAIN OUTCOME MEASURES: Proportion of patients (vaccinated, not vaccinated, and ED population) up-to-date for immunizations (1) at the time of the ED visit, (2) 1 day later, and (3) 6 months later. RESULTS: Two thirds of the patients in each ED had Medicaid, and one tenth were uninsured. At the time of the ED visit, 20% of the vaccinated children in each ED were actually up-to-date and were unnecessarily vaccinated; 74% (Manhattan ED) and 72% (Bronx ED) of the not vaccinated children were up-to-date (the remainder were later determined to have been eligible for vaccinations). One day after the ED visit, and 6 months later, the immunization rates of the vaccinated and not vaccinated children were similar. The results of the weighted analysis were as follows: for the entire ED population screened for immunization status, compared with up-to-date rates at the time of the ED visit, rates 1 day later were 11% (Manhattan ED) and 8% (Bronx ED) higher in each ED (P < .05); and rates 6 months later were the same in the Manhattan ED and 10% lower in the Bronx ED (P < .01). Eighteen percent of all children screened for immunization status were vaccinated; 10 to 15 children were screened and 2 to 4 children were vaccinated per 8-hour ED shift. CONCLUSIONS: This ED immunization program temporarily improved the immunization rates of the ED population, but substantial personnel time was required to achieve these small gains. Urban ED immunization programs are unlikely to be cost-effective.     

Immunogenicity study of Haemophilus influenzae type B conjugate vaccine in Indian infants

OBJECTIVE: To assess the immunogenicity in Indian infants to Haemophilus influenzae b oligosaccharide conjugate vaccine (HbOC). DESIGN: Prospective multicenter study. SETTING: Pediatric Out Patient Department of general hospitals in Pune and Mumbai. SUBJECTS: 124 full term healthy infants brought for routine DPT/OPV immunization. METHODS: Infants were administered 3 doses of 0.5 ml of HbOC, on the same day as their DPT/OPV immunization, injected intramuscularly on the limb opposite to that where DPT vaccine was administered. Data on local reactions and general symptoms was collected for three days after every dose. The children had their blood collected for assay of anti PRP (polyribosil ribitol phosphate) antibody titers, along with the first injection and one month after the third injection. One hundred and three infants completed the study protocol with two blood collections. RESULTS: The initial geometric mean titers (GMT) of 0.124 mcg/ml rose by 37 times to 4.552 mcg/ml. Ninety eight children (95.1%) had a final titer of > or = 0.15 mcg/ml, the minimum level associated with protection, and 77 children (74.8%) had a final level of > or = 1.0 mcg/ml, a level associated with long term protection. CONCLUSION: HbOC is immunogenic in Indian infants when used as per the locally recommended DPT/OPV immunization schedule.     

Adverse events after school leavers received combined tetanus and low dose diphtheria vaccine

Since October 1994, children in the United Kingdom have been offered tetanus vaccine combined with a low dose of diphtheria vaccine (Td) at the age of 15 to 18 years. It is recommended that schoolchildren who have already received a booster of tetanus vaccine at the time of an injury should be given low dose diphtheria vaccine alone. When this vaccine is not available, however, it is recommended that Td vaccine should be given to all children. This study was performed to compare the frequency of adverse events after Td vaccine in 15 year old children with and without a history of an additional tetanus booster in the preceding 10 years. Two hundred and sixty-five children were followed up-52 pupils (20%) with a history of an additional tetanus booster, 157 (59%) with no such history, and 56 (21%) whose history was unclear. Mild local reactions were common and occurred more commonly in children with a history of an additional tetanus booster. Twenty-three pupils (44%) who had received an additional tetanus booster had swelling over 2 cm diameter at the injection site, compared with only 39 (25%) of those with no such history (p < 0.013). Systemic symptoms were equally unusual in both groups. Only three children experienced symptoms attributed to vaccine that were severe enough for them to miss school or attend a doctor; and none of these had received an additional tetanus booster. We conclude that, in the absence of a supply of low dose diphtheria vaccine, offering Td vaccine to children with a history of additional tetanus booster is an acceptable policy.     

Antibody and cell-mediated immune responses to booster immunization with a new acellular pertussis vaccine in school children

235 healthy 10-12 years old school children were randomly immunized with either a booster dose of diphtheria-tetanus-acellular pertussis (dTap) or diphtheria-tetanus (dT) vaccine. For this booster immunization designed for school children and adults, the quantities of Bordetella pertussis antigens in the dTap vaccine had been reduced to one third of those of the Infanrix vaccine (SmithKline Beecham) commonly used for infants. IgG antibodies and cell-mediated immune (CMI) responses to pertussis toxin (PT), pertactin (PRN) and filamentous hemagglutinin (FHA) were assessed by an enzyme immunosorbent assay and in vitro proliferation of peripheral blood mononuclear cells, respectively. Before immunization, 55%, 80% and 99% of children had detectable serum IgG antibodies to PT, PRN and FHA, whereas CMI response was found in 35%, 27% and 50% of children, respectively. After immunization, a 20-30-fold increase in geometric mean level (GML) of antibodies to the pertussis antigens occurred and CMI response to PT, PRN and FHA was seen in 88%, 94% and 100% of children, respectively. Adverse reactions following the immunization were rare. The results show that booster immunization with an acellular pertussis vaccine with reduced concentrations of antigens induces both antibody and CMI responses and support further studies of this pertussis vaccine in school children.     

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.     

Antibody responses in serum and lung to intranasal immunization with Haemophilus influenzae type b polysaccharide conjugated to cholera toxin B subunit and tetanus toxoid

AIM: Cholera toxin B subunit (CTB) has previously been used as a mucosal carrier for various vaccine candidate antigens. The objective of this study was to see if coupling a bacterial polysaccharide, Haemophilus influenzae type b capsular polysaccharide (HibCPS), to CTB, either directly or through prior coupling to tetanus toxoid (TT), would improve the immunogenicity of HibCPS after nasal immunization. METHODS: HibCPS was conjugated to CTB, TT or via TT to CTB, using glutaraldehyde or 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDAC) and N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The conjugates were characterized and used for intranasal (IN) and subcutaneous (SC) immunizations of mice. The anti-Hib, -TT and -CTB antibody titers in serum and lungs after the immunizations were measured with ELISA. RESULTS: The HibCTB was poorly immunogenic both given IN and SC compared with HibTT and HibTTCTB, probably because of inefficient coupling. In contrast, the conjugation of CTB to the HibTT conjugate resulted in a preparation which was superior both to the HibTT and the HibCTB conjugates in inducing local IgA and IgG anti-HibCPS antibodies in the lungs. The anti-HibCPS serum IgG titers after IN immunization with the HibTTCTB conjugate were similar to the titers after IN immunization with HibTT, or SC immunization with a commercial HibCRM conjugate vaccine. In contrast to the other conjugates, the HibTTCTB conjugate also gave rise to anti-Hib serum IgA titers. CONCLUSION: We conclude that appropriate conjugation to CTB increases the mucosal immunogenicity of HibCPS, and that intranasal immunization with such a conjugate can give rise to both local and systemic anti-HibCPS antibody responses.     

Safety and efficacy of purified Vero cell rabies vaccine given intramuscularly and intradermally. (Results of a prospective randomized trial)

OBJECTIVES: To determine adverse reactions as a result of pre- and post-exposure rabies vaccination, using the conventional intramuscular, and reduced dose intradermal regimens and purified Vero cell rabies vaccine. DESIGN: A prospective and randomized study of patients exposed to rabies and of subjects in need of pre-exposure rabies vaccination. SETTING: A metropolitan rabies control center in a canine rabies endemic country. PATIENTS: 1198 subjects were recruited between May, 1994 and March, 1996. They were divided into four groups. Patients with suspected or proven rabies exposures were given the vaccine intramuscularly using the conventional regimen, or intradermally using the World Health Organization approved Thai Red Cross schedule. Human or equine rabies immune globulin was administered where indicated. Pre-exposure and post-exposure vaccine recipients were divided randomly into two groups each and given the vaccine either by the intramuscular or intradermal schedules. MEASUREMENTS: All local and systemic adverse reactions were recorded and statistically analyzed. RESULTS: Pruritus at injection sites was the only significant local reaction. It was more common in the intradermal groups. Low-grade fever, the only significant adverse systemic event, was more common in the intramuscular groups and was noted in 8% of all subjects. Eighty-four patients bitten by proven rabid animals were found to be alive and well 3 years later. Forty-four of these had received the intramuscular and 40 the intradermal postexposure regimens with human or equine immune globulin injected into wounds on the first day of treatment. CONCLUSIONS: Purified Vero cell rabies vaccine is safe, carries a very low adverse reaction rate and is effective in preventing rabies in severely exposed subjects when used with human or equine rabies immune globulin.     

Serum and egg yolk IgG antibody titers from laying chickens vaccinated with Pasteurella multocida

Through determining the serum and egg yolk antibody titers in immunized laying hens to Pasteurella multocida regularly, the growth-decline trend of the egg yolk antibody levels was found to be similar to that of the serum antibody levels (r = 0.94), but the growth and decline of the egg yolk antibody seemed to be delayed 3-6 days compared with that of the serum antibody, and the egg yolk antibody titers were generally lower than those of the serum antibody (P < 0.01). Serum and egg yolk antibody levels declined 3 and 6 days, respectively, after booster immunizations. The higher the antibody levels were before booster immunization, the more they declined.