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Combined vaccine regimen based on parenteral priming with a DNA vaccine and administration of an oral booster consisting of a recombinant Salmonella enterica serovar Typhimurium vaccine strain for immunization against infection with human-derived enterotoxigenic Escherichia coli strains.

Repeated evidence has demonstrated that combined primer-booster immunization regimens can improve both secreted and humoral immune responses to antigens derived from viral, bacterial, and parasitic pathogens. For the present work, we evaluated the synergic serum immunoglobulin G (IgG) and fecal IgA antibody responses elicited in BALB/c mice who were intramuscularly primed with a DNA vaccine, pRECFA, followed by oral boosting with an attenuated Salmonella enterica serovar Typhimurium vaccine (HG3) strain, with both vaccines encoding the structural subunit (CfaB) of the CFA/I fimbriae produced by human-derived enterotoxigenic Escherichia coli (ETEC) strains. The immunological properties of the vaccine regimen were evaluated according to the order of the administered vaccines, the nature of the oral antigen carrier, the age of the vaccinated animals, the interval between the priming and boosting doses, and the amount of injected DNA. The production of gamma interferon and the IgG2a subclass in serum indicated that mice immunized with the primer-booster regimen developed prevailing type 1 T-cell-dependent immune responses. The synergic effect of the vaccine regimen on the induced antibody responses was also revealed by its ability to block the adhesive properties of CFA/I fimbriae expressed by live bacteria, as shown by the inhibition of Caco-2 cell and human erythrocyte binding. Moreover, DBA2 newborn mice were protected from lethal challenges with a CFA/I+ ETEC strain after the incubation of live bacteria with serum samples harvested from mice who were subjected to the primer-booster regimen. We propose, therefore, that the DNA primer-Salmonella booster regimen represents an alternative for the development of vaccines requiring both mucosal and systemic antibody responses for immunological protection.

Animals↗

An evaluation of second generation tissue culture rabies vaccines for use in man: a four-vaccine comparative immunogenicity study using a pre-exposure vaccination schedule and an abbreviated 2-1-1 postexposure schedule.

In a double-blind comparative trial the immunogenicity of three new tissue culture rabies vaccines was evaluated, using a commercial human diploid cell vaccine (HDCV) lot as the reference. Two different vaccination regimens, a pre-exposure schedule, and an abbreviated 2-1-1 postexposure schedule (two doses of the vaccine applied bilaterally on day 0, with subsequent single doses given on days 7 and 21) were employed. In both, two of the new vaccines, purified chick embryo cell vaccine and purified Vero rabies vaccine, induced an antibody response equivalent to that of HDCV, while the geometric mean titres for the fetal bovine kidney cell vaccine were somewhat lower. The 2-1-1 regimen, a candidate regimen for economical rabies postexposure treatment, evoked a rapid and high titre antibody response with all four vaccines, peaking on day 14.

Adult↗

Measles vaccine efficacy: influence of age at vaccination vs. duration of time since vaccination.

To evaluate the recent decision of the Advisory Committee on Immunization Practice to increase the recommended age for initial measles vaccination from 12 to 15 months, we carried out a case control study of vaccine failure in a recent measles epidemic. Compared to children vaccinated at ages 15 months or older, we found an increased risk of vaccine failure among those vaccinated at 12 to 14 months (relative risk = 19.2, 95% confidence interval = 4.6 to 80.1). In order to sort out the influence of age at vaccination from elapsed time since vaccination, we subjected the data to discriminant analysis. Age at vaccination subsumed all of the effect of duration of time since vaccination. Thus, we find no evidence of waning immunity over time.

Age Factors↗

Safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate) administered concurrently or combined with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine to healthy infants at two, four and six months of age.

The safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate (PRP-T) administered concurrently in separate sites or mixed in the same syringe with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine were assessed in 439 infants at 2, 4 and 6 months of age. The proportions with local redness, tenderness and swelling in the separate and combined groups were 18% vs. 11% (P < 0.001), 27% vs. 24% and 15% vs. 13%, respectively. Systemic reactions occurred at similar rates in both groups. The combined vaccine induced tetanus and diphtheria antitoxin titers > or = 0.01 IU/ml in 99.5 and 99.1% of infants, pertussis agglutinin titers > or = 64 in 92.4%, anti-polyribosylribitol phosphate titers > or = 0.15 microgram/ml in 93.8% and > or = 1.0 microgram/ml in 75% and polio-neutralizing titers > or = 8 in > 98% of infants. However, antibody concentrations to PRP-T, some pertussis antigens and tetanus toxoid were significantly lower after combined than after separate injections of DPT/diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine and PRP-T. The clinical significance of these differences is not known, but the interactions observed among the components of the pentavalent vaccine may be of concern because they might influence antibody persistence until the fourth dose is administered.

Diphtheria-Tetanus-Pertussis Vaccine↗

Efficiency of the incorporation of the hepatitis A vaccine as a combined A+B vaccine to the hepatitis B vaccination programme of preadolescents in schools.

In 1998, the Department of Health of Catalonia (Spain) began universal vaccination of preadolescents against hepatitis A by replacing the simple hepatitis B vaccine with a combined hepatitis A+B vaccine. Economic analyses were made of the two alternative strategies: to continue with the simple hepatitis B vaccination or to replace the simple vaccine with a combined hepatitis A+B vaccine. The analysis was made from the societal perspective and the time horizon considered was 25 years. In the base case, (estimated annual hepatitis A incidence of 15 per 100,000 and incremental price of the hepatitis A+B vaccine over the simple hepatitis B vaccine of 1.98) the net present value of the programme was positive (+533,708) and the benefit-cost ratio was 2.58. If the estimated disease incidence were reduced by half, the programme would still be efficient.

Child↗

Haemophilus influenzae type b vaccine: reconstitution of lyophilised PRP-T vaccine with a pertussis-containing paediatric combination vaccine, or a change in the primary series immunisation schedule, may modify the serum anti-PRP antibody responses.

Immunogenicity data obtained after primary series immunisations against Haemophilus influenzae type b (Hib), using a vaccine prepared by conjugating the capsular polysaccharide of Hib to tetanus toxoid (ActHIB), were compiled from 146 study groups comprising 85 clinical trials or vaccination programs conducted between 1987 and 1999. ActHIB was administered as a monovalent lyophilised vaccine, injected either in association with another paediatric vaccine (at separate administration sites) or in combination (where the different vaccines are mixed together in the same syringe before injection). Review of these data reveals two trends. First, PRP-T vaccine, given either alone or in combination with DTwcP, resulted in a stronger anti-PRP serum antibody response than when PRP-T was combined with DTacP vaccine. Second, an accelerated (i.e. one-month interval) immunisation schedule tended to induce a poorer anti-PRP antibody response than did the more widely spaced, standard inoculation schedules. Although an in-depth analysis of these over 11000 study subjects on an individual basis with multivariate analysis or multifactorial statistical methods might eventually provide working hypotheses to fully understand these phenomenon, the various licensed, PRP-T-containing paediatric combination vaccines have proved to be clinically effective.

Antibodies, Bacterial↗

Efficacy of live B1 or Ulster 2C Newcastle disease vaccines simultaneously vaccinated with inactivated oil adjuvant vaccine for protection of Newcastle disease virus in broiler chickens.

Two hundred, one-day-old broiler chicks were divided into groups 1, 2 and 3 containing 60, 70 and 70 chicks, respectively. The groups were divided into subgroups of 10 chicks that were vaccinated according to the following scheme: group 1 unvaccinated control, group 2 vaccinated subcutaneously at 1 day old with inactivated oil adjuvant vaccine (IOAV) in combination with live B1 vaccine. Group 3 was vaccinated in the same mode as group 2 with IOAV and live Ulster 2C vaccine. All birds were challenged when they were 28 days old. Mortality rate, body weight gain and feed conversion ratio (FCR) were monitored before and after challenge. All the chickens in group 1 died, indicating that there was no disease resistance of this unvaccinated control group of chickens. Conversely, the monitored disease resistance of chickens in groups 2 and 3 was 68.57% +/- 18.64 and 88.57% +/- 9.00, respectively (P < 0.05). The morbidity of chickens in groups 2 and 3 was 37.89% +/- 14.36 and 14.76% +/- 12.40, respectively (P < 0.05). The body weight gain, feed intake and FCR of group 3 were significantly better than those of group 2 (P < 0.05) during 1-42 days old. The simultaneous vaccination with B1 or Ulster 2C and IOAV of 1-day-old chicks gave some protection of 28-day-old broilers without a booster vaccination.

Animals↗

Antibody persistence against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b (Hib) in 5-6-year-old children after primary vaccination and first booster with a pentavalent combined acellular pertussis vaccine: immunogenicity and tolerance of a tetravalent combined acellular pertussis vaccine given as a second booster.

UNLABELLED: The main objective of this study was to assess in 5-6-year-old French children (n=234) the persistence of antibodies induced by a primary series vaccination (at 2-4 months of age) and a first booster (at 12-16 months of age) with a pentavalent two-component acellular pertussis combined vaccine (DTacP-IPV-Hib; Pentavac). The second objective was to evaluate in these 5-6-year-old French children the safety and the immunogenicity of a tetravalent acellular pertussis combined vaccine (DTacP-IPV; Tetravac) given as second booster. RESULTS: Seroprotective antibody levels against diphtheria, tetanus, types 1-3 poliomyelitis and PRP were maintained 4-5 years after primary-vaccination and first booster with Pentavac. As expected, anti-PT antibodies levels were low, suggesting that children were not colonised by Bordetella pertussis. The second booster with Tetravac was well tolerated and elicited a strong booster response for all antigens. CONCLUSION: acellular pertussis combined vaccine, used in primary-vaccination, could be considered as having the same priming effect and the same efficacy as whole cell pertussis vaccine.

Antibodies↗

Absence of a significant interaction between a Haemophilus influenzae conjugate vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine in the same syringe and inactivated polio vaccine.

BACKGROUND: We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after three doses of a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine (DTaP) combined with a PRP-tetanus conjugate (PRP-T) in infants randomized to receive oral polio vaccine (OPV) or inactivated polio vaccine (IPV). The polio vaccine was given separately at the same visit. METHODS: Three hundred fifty-six infants from pediatric practices in suburban Chicago and New Orleans were randomized into two groups. Group A received OPV at 2 and 4 months of age; Group B received IPV at 2 and 4 months of age. Both groups received DTaP/PRP-T at 2, 4 and 6 months of age and hepatitis B vaccine at 2 and 4 months of age. A serum sample was obtained before immunization (age 2 months) and 1 month after 3 doses of DTaP/PRP-T (age 7 months). Sera were assayed for antibody responses to all relevant vaccine antigens. RESULTS: No significant vaccine antigen interference was found when polio immunization was provided by IPV or OPV for anti-PRP, diphtheria, tetanus or pertussis antibodies. OPV recipients had a significantly higher mean antibody response to serotype 1 (P = 0.03) and 2 (P = 0.0001) poliovirus. CONCLUSION: Whether polio immunization was accomplished with IPV or OPV did not significantly influence the antibody responses in sera obtained at 7 months of age for anti-PRP, anti-diphtheria and anti-tetanus toxoid antibodies and antibodies to pertussis antigens, when DTaP/PRP-T was given in the primary series.

Antibodies, Bacterial↗

Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS).

PURPOSE: To assess the safety of a licensed anthrax vaccine given to nearly 400,000 US military personnel, reports of adverse events (AEs) submitted to the Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated medically. METHODS: The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of private-sector physicians and other scientists, reviewed 602 VAERS reports using a Delphic approach (structured expert consensus) to assess the causal relationship between vaccination and the reported AEs and sought to identify unexpected patterns in the occurrence of medically important events. Reports were entered into a database and used to profile AEs with respect to person, type/location, relative frequency, severity/impact, concomitant illness or receipt of other drugs or vaccines, and vaccine lot. RESULTS: Nearly half the reports noted a local injection-site AE, with more than one-third of these involving a moderate to large degree of inflammation. Six events qualified as serious AEs (SAEs), and all were judged to be certain consequences of vaccination. Three-quarters of the reports cited a systemic AE (most common: flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual medically important events were judged possibly or probably due to vaccine (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2), bronchiolitis obliterans organizing pneumonia). CONCLUSIONS: Since some cases of local inflammation involved distal paresthesia, AVEC recommends giving subcutaneous injections of AVA over the inferior deltoid instead of the triceps to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation of VAERS reports does not suggest a high frequency or unusual pattern of serious or other medically important AEs.

Adolescent↗

Clinical responses to smallpox vaccine in vaccinia-naive and previously vaccinated populations: undiluted and diluted Lancy-Vaxina vaccine in a single-blind, randomized, prospective trial.

We conducted a single-blind, randomized trial of 2 dilutions (1:1 or 1:10) of Lancy-Vaxina vaccine (Berna Biotech) in vaccinia-naive persons (n=36) and persons previously vaccinated >25 years ago (n=76). All vaccinees responded successfully to the vaccination. There were no significant differences in the size of the skin lesions, the number of adverse events, the amount of viral shedding, or the level of antibody responses between the undiluted (n=56) and diluted (n = 56) vaccine groups. Compared with vaccinia-naive persons, previously vaccinated persons exhibited significantly smaller and more rapidly evolving skin lesions and fewer adverse events. Previously vaccinated persons had significantly higher neutralizing antibody levels before the administration of the study vaccine than vaccinia-naive persons, and viral shedding from lesions in previously vaccinated persons was lower and diminished more rapidly than from lesions in vaccinia-naive persons.

Adult↗

Sustained transmission of mumps in a highly vaccinated population: assessment of primary vaccine failure and waning vaccine-induced immunity.

From January to July 1991, an outbreak of mumps occurred in Maury County, Tennessee. At the primarily affected high school, where 98% of students and all but 1 student with mumps had been vaccinated before the outbreak, 68 mumps cases occurred among 1116 students (attack rate, 6.1%). Students vaccinated before 1988 (the first year mumps vaccination was required for school attendance in Tennessee) may have been at greater risk of mumps than those vaccinated later (65[6.1%] of 1001 vs. 2[2.2%] of 89; risk ratio, 2.9; 95% confidence interval, 0.7-11.6). Of 13 persons with confirmed mumps who underwent serologic testing, 3 lacked IgM antibody in well-timed acute- and convalescent-phase serum specimens. Vaccine failure accounted for a sustained mumps outbreak in a highly vaccinated population. Most mumps cases were attributable to primary vaccine failure. It is possible that waning vaccine-induced immunity also played a role.

Adolescent↗

Analyses of adverse reactions to diphtheria and tetanus toxoids and pertussis vaccine by vaccine lot, endotoxin content, pertussis vaccine potency and percentage of mouse weight gain.

We investigated the rates of local and systemic reactions following 9920 diphtheria-tetanus toxoids-pertussis immunizations from 25 lots of commercially available, United States-licensed diphtheria-tetanus toxoids-pertussis adsorbed vaccines from four manufacturers as a function of vaccine lot, endotoxin content, pertussis vaccine potency and percent of mouse weight gain. There were significant differences between the rates of reactions by lot for all local and systemic reactions except convulsions and hypotonic hyporesponsive episodes. For these latter reactions there were insufficient cases for analyses. P was less than 0.0001 for local reactions, fever, drowsiness, fretfulness, anorexia and screaming and 0.017 for vomiting. No single lot was associated with the highest or lowest rate of reactions for more than 3 of the 11 reactions. There was a significant positive association of endotoxin unit (EU) content and the percent of vaccine recipients who developed fever (P = 0.004). Fever increased in frequency from 20.6% of children immunized with vaccine lots that contained 2500 EU to 55.1% of children immunized with vaccine lots containing 40,000 EU. There were significant positive associations of all local reactions and pertussis vaccine potency (P = 0.0004), and percent of mouse weight gain (P less than 0.0001). There was also a positive association of percent mouse weight gain and persistent screaming (P = 0.001). However, for the majority of reactions there was no clinically meaningful associations between reaction rates and the biological properties of the vaccine studied.

Animals↗

Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine.

Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.

Antibodies, Viral↗

Vaccination against Marek's disease and infectious bursal disease. I. Development of a bivalent live vaccine by co-cultivating turkey herpesvirus and infectious bursal disease vaccine viruses in chicken embryo fibroblast monolayers.

Vaccine viruses of Marek's disease (MD), the FC-126 strain of the herpesvirus of turkeys (HVT), and infectious bursal disease (IBD), the Bursa-Vac-M strain of IBD virus (IBDV), were propagated in the same chicken embryo fibroblast (CEF) monolayers by superinfection. Co-infection of the two viruses in the same CEF culture or in a single cell can be demonstrated by staining with acridine orange and by electron microscopy.l This study was conducted with a superinfected live bivalent vaccine (HVT/IBDV) in one-day-old specific pathogen-free (SPF) and conventional White Leghorn (CWL) chicks. Chickens vaccinated with HVT/IBDV produced persistent HVT viremia for at least 6 weeks postvaccination; significantly higher IBD virus neutralizing antibody levels were observed for the entire 8-week experimental period when compared to unvaccinated controls. Differences between virus neutralizing antibody titers stimulated by HVT/IBDV and IBDV alone were not statistically significant in SPF chickens; however, due to maternal antibody there were some significant differences in CWL chickens. Both the HVT/IBDV bivalent vaccine and the monovalent IBDV vaccine protected the chickens against challenge with virulent IBDV. Based on microscopic lesions and bursa: body weight indexes, challenge of vaccinated chickens with virulent IBDV caused no atrophy in the bursa of Fabricius, but severe tissue destruction was observed in unvaccinated challenged controls. Chickens vaccinated with HVT/IBDV vaccine or with HVT alone were effectively protected against MD when compared to the controls.

Animals↗

[Specific immune response to vaccination with an inactivated flue vaccine depending on prevaccine status and age of the person vaccinated].

Specific antibody immune response to vaccination with commercial inactivated trivalent vaccine A(H1N1) + A(H3N2) + B (IgA, IgG, IgG, subclasses G1, G3, G4, and accumulation of antiCD8) was studied in subjects aged 20-95 years. The initial immune status before vaccination is significant for a positive immune response to the vaccine. Subjects responding to immunization by an increment in specific IgG had a much lower prevaccination level of these antibodies than subjects without these Ig conversion. Antibody immune response to vaccination depended on patient's age. All vaccinees aged 20-25 years developed an increment in IgG to at least one of influenza antigens used. Specific postvaccinal immune response to inactivated influenza vaccine included accumulation of G1, G3, and A antibodies, but not G4 or E antibodies. This latter fact suggests the absence of sensitizing effect of vaccination. In elderly subjects an increment in G1, G3, and A antibodies may not involve an increase in the total level of IgG. In part of elderly subjects secretion of specific antibodies was observed in the presence of increased concentration of antilymphocytic antibodies (antiCD8), indicating a possibility of autoimmune reactions in subjects of this age after injection of inactivated influenza vaccine.

Adult↗

Rhesus diploid rabies vaccine (adsorbed), a new rabies vaccine. Results of initial clinical studies of preexposure vaccination.

To meet the need for a safe, efficacious, and low-cost rabies vaccination program, the Michigan Department of Public Health developed a new rabies vaccine: rhesus diploid rabies vaccine, adsorbed (RDRV). Initial clinical studies were conducted in 534 volunteers using preexposure protocols consisting of two injections of RDRV given 1, 2, or 4 weeks apart. This new rabies vaccine induced an excellent rabies virus antibody response two to three weeks after vaccination: antibody levels were superior to those reported after duck embryo rabies vaccine and were similar to those reported with human diploid rabies vaccine. In addition, vaccination with RDRV was associated with an acceptable level of local and constitutional symptoms.

Adolescent↗

Vaccination against hepatitis B in a general hospital in Israel: antibody level before vaccination and immunogenicity of vaccine.

We offered hepatitis B vaccine (Heptavax B) to 809 of the health care personnel of a 650-bed regional hospital; 290 accepted the offer. Anti-HBs measurement was done by enzyme immunoassay (AUSAB EIA, Abbott, UK) and expressed in mIU/ml. Seroconversion was determined at a level of 2.1 mIU/ml. Of 290 employees 58 (20%) were found positive for hepatitis B antibodies before vaccination. Of the laboratory technicians, 40.9% were found positive for antibodies before vaccination, as were 26.5% of nurses and 10.9% of physicians. Among vaccine recipients 35.8% responded after the first dose, 86.6% after the second and 92.7% after the third. Seventeen workers (7.3%) were nonresponders, of whom 14 received the whole vaccine series. There was no difference in immune responses to the vaccine between men and women. The present study confirms the relatively high prevalence of HBV infection in health care workers. Furthermore, vaccination of employees has been highly effective and well tolerated. The present data, therefore, support the introduction of active vaccination against HBV in health care workers in Israel.

Adult↗