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[Comparative study on antibody levels of vaccination group and control group after 4 years of immunized with type B inactivated vaccine against hemorrhagic fever with renal syndrome].

OBJECTIVE: To compare the antibody level of vaccine group and control group in a randomized, controlled trial of type B inactivated vaccine against hemorrhagic fever with renal syndrome(HFRS) in Jiande County of Zhejiang Province and to find out if there is enhancement of subclinical infection about type B inactivated vaccine against HFRS. METHODS: The number of sera collected (July 1994-July 1998) in vaccine group immunized type B inactivated vaccine against HFRS and control group were 305 and 283 persons in Jiande County respectively, and indirect immunofluorescent antibody method(IFAT) was used for testing the titer of HFRS IgG in sera. The cut-off values were determined on IFA titer of the second sera in control group with positive and negative IFA before vaccine was given respectively, and the subclinical infection of positive and negative IFA of the first sera in vaccine group was evaluated. RESULTS: When taking different cut-off values of subclinical infection, there were no statistical differences in HFRS IFA positive rates between vaccine group and control group of positive IFA in the first sera. In vaccine group and control group of negative IFA before vaccine given, also the IFA positive rates were not statistically different in these groups. There were no statistical differences of IFA GMT and IFA sero-negative rate between vaccine group and control group. CONCLUSIONS: The investigation showed there was no statistical difference in antibody level between vaccine group and control group, so there could not be enhancement of subclinical infection of vaccine group receiving type B inactivated vaccine against HFRS.

Adolescent↗

A one year followup of chronic arthritis following rubella and hepatitis B vaccination based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database.

OBJECTIVES: This analysis examined the incidence rate of chronic arthritis adverse reactions reported following adult rubella and hepatitis B vaccinations. In this analysis, etiologic mechanisms for chronic arthritis following adult rubella and hepatitis B vaccines were also explored. METHODS: The Vaccine Adverse Events Reporting System (VAERS) database was analyzed for the incidence rate of reported cases of chronic arthritis in comparison to Tetanus-diphtheria (Td) and tetanus toxoid adult vaccine control groups. RESULTS: Chronic arthritis adverse reactions following adult rubella vaccination were primarily reported in females (female/male ratio = 3.0), at about 45 years-old, and at a mean onset time of 10-11 days following vaccination. Chronic arthritis adverse reactions following adult hepatitis B vaccination were also primarily reported in females(female/male ratio = 3.5), at about 33 years-old, and with a mean onset time of 16 days following vaccination. The incidence rates of chronic arthritis following adult rubella and adult hepatitis B vaccinations were statistically significantly increased, by chi 2 analysis, in comparison to the adult vaccine control groups. The attributable risk of chronic arthritis following adult rubella vaccine ranged from 32 to 53 and from 5.1 to 9.0 following adult hepatitis B vaccine in comparison to the adult vaccine control groups. CONCLUSION: This study revealed that adult rubella and adult hepatitis B vaccines were statistically associated with chronic arthritis which persisted for at least one year. The etiology for these adverse reactions may involve autoimmune mechanisms. Furthermore, potential biases in the reporting rates of adverse reactions to VAERS were not observed.

Adult↗

Evaluation in macaques of HIV-1 DNA vaccines containing primate CpG motifs and fowlpoxvirus vaccines co-expressing IFNgamma or IL-12.

Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFNgamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1.

AIDS Vaccines↗

Cost effectiveness of adding 7-valent pneumococcal conjugate (PCV-7) vaccine to the Norwegian childhood vaccination program.

BACKGROUND: Streptococcus pneumoniae is a frequent bacterial cause of serious infections that may cause permanent sequelae and death. A 7-valent conjugate vaccine may reduce the incidence of pneumococcal disease, but some previous studies have questioned the cost-effectiveness of the vaccine. The aim of this study was to estimate costs and health consequences of adding this pneumococcal vaccine to the Norwegian childhood vaccination programme, taking the possibility of herd immunity into account. METHODS: We developed a simulation model (Markov-model) using data on the risk of pneumococcal disease in Norway, the efficacy of the vaccine as observed in clinical trials from other countries and adjusted for serotype differences, the cost of the vaccine and quality of life for patients with sequelae from pneumococcal disease. The results were expressed as incremental (additional) costs (in euros; euro1.00 approximately NOK8.37), incremental life years and incremental quality adjusted life years. Four different sets of main results are presented: costs and (quality adjusted) life years, with and without indirect costs (the value of lost production due to work absenteeism) and with and without potential herd immunity (i.e. childhood vaccination protects adults against pneumococcal disease). RESULTS: When indirect costs were disregarded, and four vaccine doses used, the incremental cost per life year gained was euro153,000 when herd immunity was included, and euro311,000 when it was not. When accounting for indirect costs as well, the cost per life year gained was euro58,000 and euro124,000, respectively. Assuming that three vaccine doses provide the same protection as four, the cost per life year gained with this regimen was euro90,000 with herd immunity and euro184,000 without (when indirect costs are disregarded). If indirect costs are also included, vaccination both saves costs and gains life years. INTERPRETATION/CONCLUSION: In Norway, governmental guidelines indicate that only interventions with cost per life year of less than euro54,000 should be implemented. This implies that four dose vaccination is not cost-effective even if decision makers includes both herd immunity and indirect costs in their decisions. If three doses offer the same protection as four doses, however, vaccination would be cost-saving when indirect costs are included, but not with only herd immunity. COMMENT: In the autumn of 2005, the Norwegian Government decided to include PCV-7 in the vaccination program. This analysis was used by the Ministry of Health and Ministry of Finance during the decision process.

Bacteremia↗

IgG subclasses and avidity of antibodies to polysaccharide antigens in allogeneic BMT recipients after vaccination with pneumococcal polysaccharide and Haemophilus influenzae type b conjugate vaccines.

In a randomized study, 20 adult allogeneic BMT recipients were vaccinated at 6 months and 22 at 18 months after BMT with Haemophilus influenzae type b (Hib)-diphtheria toxoid conjugate vaccine (PRP-D), and 23 recipients at 8 months and 21 at 20 months with pneumococcal polysaccharide (Pnc PS) vaccine. IgG1 and IgG2 subclasses of Pnc PS and Hib antibodies and avidities of Pnc PS IgG antibodies were determined by EIA in sera from patients with at least a two-fold total antibody response to Pnc type 3, 6B, 19F or PRP-D. The Pnc PS vaccine induced predominantly IgG1 Pnc 3 antibody production. Anti-Pnc 6B and 19F responses were mainly IgG2. The time of the Pnc PS vaccination, at 8 or 20 months after BMT, did not influence the IgG subclass response pattern. The PRP-D vaccine induced predominantly IgG2 anti-Hib production in the patients vaccinated at 6 months after BMT. The patients vaccinated at 18 months produced IgG1 and IgG2 antibodies more evenly. The same patient was able to produce predominantly IgG1 subclass antibodies to one antigen, Pnc 3, 6B, 19F or Hib, and IgG2 antibodies to another. The avidities of anti-Pnc 6B and 19F 1 month after vaccination were similar to those before vaccination, anti-Pnc 3 avidity was lower than before vaccination but matured in 15 months. The IgG subclass distribution and avidity were similar in the patients with and without chronic GVHD. In conclusion, the IgG response to Pnc type 3 was predominantly IgG1 as in infants and IgG2 to PRP-D, Pnc 6B, and 19F as in adults. Early vaccination after BMT or the presence of chronic GVHD did not impair the quality of response to Pnc PS and PRP-D vaccines.

Adolescent↗

Benefits of combination vaccines: effective vaccination on a simplified schedule.

BACKGROUND: The number of recommended immunizations during childhood has increased significantly over the years. Today, infants receive vaccines against 11 diseases in the first 2 years of life, and may receive as many as 5 injections at a single office visit. For a number of reasons, some injections may be deferred to a later visit, thus creating a missed opportunity for vaccination. OBJECTIVE: To review benefits of pediatric combination vaccines. RESULTS: Combination vaccines that protect against several diseases, such as the new DTaP-HepB-IPV (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B [Recom-binant] and Inactivated Poliovirus Vaccine Combined) vaccine, can help to simplify the current immunization schedule. Other benefits of combination vaccines for parents and healthcare providers include decreased anxiety because of perceived reduction in pain for the infant, fewer missed opportunities to vaccinate, convenience, and decreased costs for the parent as a result of fewer office visits. Benefits of using combination vaccines in the office setting include reduced missed opportunities to vaccinate, storage of fewer vials, decreased risk of needle sticks as a result of handling fewer syringes, and potentially improved record keeping and tracking. Benefits of using combination vaccines in managed care include improved member satisfaction and lower costs because of fewer vaccine administration charges, and potentially fewer office visits. CONCLUSIONS: Combination vaccines are an effective means of decreasing the number of injections and simplifying the immunization schedule, thus providing overall benefits to infants, parents, healthcare providers, office managers, and managed care administrators.

Diphtheria-Tetanus-Pertussis Vaccine↗

Impact of thimerosal-related changes in hepatitis B vaccine birth-dose recommendations on childhood vaccination coverage.

CONTEXT: In July 1999, the longstanding preference to begin hepatitis B vaccination of all US infants at birth was temporarily suspended because of concerns about exposure to mercury contained in the vaccine preservative thimerosal. The suspension was lifted in September 1999 when preservative-free hepatitis B vaccine became available. OBJECTIVE: To determine the effects of changes in recommendations regarding administration of a hepatitis B birth dose on vaccination coverage. DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of vaccination status of 41,589 US children born before, during, and after the recommendation to suspend the birth dose. MAIN OUTCOME MEASURES: Association between birth cohort and age at receipt of hepatitis B vaccine dose 1, and receipt by 19 months of age of all recommended vaccines. RESULTS: The proportion of US infants who received dose 1 of hepatitis B vaccine at birth declined from 47% among those born 7 to 12 months before the suspension to 11% among those born during the suspension. Birth-dose coverage remained significantly lower in the year after the suspension was lifted (23% in the first 6 months and 33% in months 7-12). Coverage with 3 doses of hepatitis B vaccine by 19 months of age declined from 88% among those born 7 to 12 months before the suspension to 81% among those born during the suspension and 85% among those born in the 6 months after the suspension, but returned to baseline levels for those born 7 to 12 months after the suspension was lifted. These reductions represent 750,000 fewer newborns vaccinated during 2000 compared with 1998, and an excess 182,000 children undervaccinated for hepatitis B at 19 months of age compared with 1998 coverage levels. Coverage with other recommended vaccinations did not decline over this time. CONCLUSIONS: Reductions in hepatitis B vaccine birth-dose coverage persisted after recommendations were made to resume previous newborn vaccination practices. Although the recommendation to complete the series by 19 months of age was never changed, infants born between July and December 1999 were less likely to have completed the series by 19 months, compared with infants born during the previous year. The lack of impact on other vaccinations suggests that public confidence in immunization remained strong.

Cohort Studies↗

Tracking vaccine lot lifecycles using reports to the vaccine adverse event reporting system (VAERS).

PURPOSE: There is currently no systematically available information available on how rapidly a specific lot of vaccine is used once distributed. We used data from reports to the Vaccine Adverse Event Reporting System (VAERS) to develop a proxy means of surveillance for the lifecycle of selected vaccine lots. METHODS: A convenience sample, consisting of selected lots of: diphtheria, tetanus, and acellular pertussis (DTaP), Haemophilus influenzae type b (Hib), Hepatitis B, and varicella vaccines, was selected for lifecycle analysis. Assuming that circulation of a vaccine lot is proportional to vaccine-specific adverse event (AE) reporting for that vaccine type, we constructed Gamma distributed usage models and compared them with lot-specific VAERS reports to estimate the actual lifecycle of lots in the system. RESULTS: Evidence of lot circulation was detected within 1-2 months, and a peak was observed 3-4 months after the vaccine release date for most of the study vaccines. Ninety percent of the vaccine doses in each lot were estimated to be used within 5-9 months of distribution. The length of time a vaccine lot was in use ranged from 5 to 17 months from earliest vaccination date. CONCLUSIONS: Our modeled and inferred administration of the selected lots of different vaccines were concordant. This method may be useful for spatial and temporal tracking of vaccine lot utilization.

Models, Theoretical↗

Effect of timing of hepatitis B vaccine doses on response to vaccine in Yucpa Indians.

In a large hepatitis B prevention programme, hepatitis B vaccine was given in standard doses to greater than 1000 susceptible Yucpa Indians between 1983 and 1985. Thirteen months after the programme began, 373 vaccine recipients were tested using commercial radioimmunoassay to titre antibody response to the vaccine. Because of logistic difficulties, only 32% had received vaccine by the recommended schedule (second and third doses at one and six months after the first, respectively). The second and third doses were received early by 4 and 31%, respectively, and 27 and 16% received these doses later than intended. Overall response to vaccine was excellent: 98% of vaccinees developed anti-HBs greater than 10 mIU (geometric mean titre 688 mIU). Multivariate analysis showed that the response to vaccination was inversely related to the age of the vaccinee and directly related to the timing of the third vaccine dose. In particular, those receiving the third vaccine dose late (greater than 7 months after the first dose) developed antibody titres two-fold higher than those receiving the third dose on schedule (p less than 0.01). The response to vaccination was not significantly related to the timing of the second dose. A satisfactory response was obtained with various schedules of dose timing, including early second and third doses, late second and third doses and late second but normal third doses. These findings suggest that the response to hepatitis B vaccine is not highly dependent on timing of vaccine doses and that modest alterations in timing of doses, such as those necessary to integrate hepatitis B vaccine with other childhood vaccines, do not affect the excellent response to this vaccine.

Adolescent↗

Vaccine independence, local competences and globalisation: lessons from the history of pertussis vaccines.

In the context of global vaccine politics 'vaccine independence' has been defined as the assumption of financial responsibility for vaccine procurement. This paper suggests 'the possibility of vaccine choice' as an alternative meaning for the term. How far does local competence in vaccine development and production provide that possibility? Coupled to the national vaccination programme, such competence enabled the Netherlands to make use of a polio vaccine (Inactivated Polio Vaccine, or IPV) that it was felt best met national needs even though the rest of the world had switched to the alternative attenuated vaccine (generally known as Oral Polio Vaccine, or OPV); by the 1970s IPV was no longer commercially available. Over the past 20 years major changes in vaccine politics have occurred. Does the earlier conclusion regarding local competence still hold? The more recent example of pertussis (or whooping cough) vaccines, where again controversy surrounds the relative merits of alternative vaccines, permits the question to be posed anew. Results of our analysis from the Netherlands suggest, first, that the pressure to conform has become greater, and second, that the taken-for-granted globalism of today's vaccine system is in need of critical examination.

Decision Making↗

The effect of random vaccine response on the vaccination coverage required to prevent epidemics.

The response people have to vaccination varies because their immune systems differ and vaccine failures occur. Here we consider the effect that a random response, independent for each vaccinee, has on the vaccination coverage required to prevent epidemics in a large community. For a community of uniformly mixing individuals an explicit expression is found for the critical vaccination coverage (CVC) and the effect of the vaccine response is determined entirely by the mean E(AB), where A and B, respectively, reflect the infectivity and susceptibility of a vaccinated individual. This result shows that the usual concept of vaccine efficacy, which focuses on the amount of protection the vaccine provides the vaccinee against infection, is not adequate to describe the requirements for preventing epidemics when vaccination affect infectivity. The estimation of E(AB) poses a problem because A and B refer to the vaccine response of the same individual. Similar results are found when there are different types of individual, but now the mean E(AB) may differ between types. However, for a community made up of households it is shown that the CVC also depends on other characteristics of the vaccine response distribution. In practice this means that estimating a single measure of vaccine effectiveness is generally not enough to determine the CVC. For a specific community of households it is found that the vaccination coverage required to prevent epidemics decreases as the variation in the vaccine response increases.

Disease Outbreaks↗

Studies with inactivated equine influenza vaccine. 1. Serological responses of ponies to graded doses of vaccine.

Serological responses to three bivalent aqueous equine influenza vaccines of different potency and an adjuvanted bivalent vaccine containing inactivated A/equine/Prague/56 (H7N7) and A/equine/Miami/63 (H3N8) viruses, were examined in seronegative ponies. Potencies of the vaccines, measured by single-radial-diffusion tests, ranged from 4 to 56 micrograms of haemagglutinin (HA) antigen activity/virus strain per dose. Serological responses to vaccination were examined by haemagglutination-inhibition (HI) and single-radial-haemolysis (SRH) tests. Four weeks after a primary dose, HI responses to both vaccine viruses were barely detectable; after a second dose the HI responses to A/Miami/63 virus were low or undetectable but HI responses to A/Prague/56 virus were higher (17/20 ponies with titres greater than or equal to 1:16). In contrast SRH tests revealed dose-related antibody responses to both virus strains after one and two vaccine doses; levels after the second dose were 2- to 5-fold higher than after the primary dose. Highest post-vaccination antibody titres were obtained with the adjuvanted vaccine which contained 2- to 4-fold less antigen (13-23 micrograms HA) than the most potent aqueous vaccine. Post-vaccination antibody reacted well in SRH tests with recent antigenic variants of equine influenza virus. A remarkable finding was the high rate of decline in antibody, detected by HI or SRH tests, following one or two doses of vaccine. Even in animals with the highest post-vaccine antibody levels 2-4 weeks after a booster dose, antibody levels had declined to low or indetectable levels 14 weeks later. The low antibody titres detected at 14-32 weeks after vaccination were nevertheless vaccine dose-related.

Animals↗

Adult hepatitis B vaccination using a novel triple antigen recombinant vaccine.

Present hepatitis B vaccines use multidose prolonged regimens, which even healthcare workers at risk do not always complete. Moreover, when vaccination is completed there remain some who fail to achieve adequate protection. The protection of adults at risk could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available. Vaccine-naive adults were randomized to vaccination with either Engerix-B (SmithKline Biologicals, Rixensart, Belgium) or a novel triple antigen (S, pre-S1, and pre-S2) recombinant vaccine (Hepacare; Medeva Pharma Plc, Speke, UK). The primary efficacy parameter was the degree of seroprotection 6 or 7 months (26 +/- 2 weeks) after beginning vaccination. A total of 304 adults entered the study. Of these, 16 failed to complete the study (9 on Hepacare and 7 on Engerix-B). With the Engerix-B standard (0, 1, 6) regimen, 88% of subjects were protected by month 7, whereas with the triple antigen vaccine a 2-dose regimen (0, 1) provided equivalent protection (91%) within 6 months and a 3-dose (0, 1, 6) regimen was significantly superior (98% seroprotected by 7 months after starting vaccination P <.001). With adults at risk for a suboptimal response (i.e., older adults, the obese, men, and smokers) the triple antigen vaccine produced a greater degree of protection. The vaccines had similar safety profiles. Both vaccines were well tolerated. In healthy normal adults, a triple antigen hepatitis B vaccine containing S and pre-S antigens produced an enhanced immunologic response and was as effective as a 2- and 3-dose regimen.

Adult↗

Pneumococcal vaccination in HIV-1-infected adults in Uganda: humoral response and two vaccine failures.

OBJECTIVES: To assess the feasibility of establishing a pneumococcal vaccine trial among HIV-1-infected adults in Uganda and to characterize their responses to 23-valent pneumococcal polysaccharide vaccine. DESIGN: An open-label pilot trial to assess recruitment and compliance of HIV-1-infected adults in Uganda to vaccination and to determine the immunogenicity of the vaccine. SETTING: A community clinic for HIV-1-infected adults in Entebbe, Uganda. METHODS: Levels of capsule-specific IgG to four common vaccine capsular serotypes were measured before vaccination and 1 month after vaccination. Subsequent rates of disease episodes and deaths, and immunologic responses in two vaccine failures, were followed. RESULTS: One month after-vaccination, both HIV-1-infected (n = 77) and seronegative control subjects (n = 10) demonstrated a significant rise in capsule-specific immunoglobulin G (IgG) for three of four serotypes tested, but levels were significantly lower among HIV-1-infected patients. In 149 patient-years of follow-up, two (2.6%) developed pneumococcal pneumonia, one bacteremic with serotype 1 and one non-bacteremic with serotype 13, a non-vaccine serotype; both patients showed inadequate killing of the organism in vitro. In this same follow-up period, 29 (38%) patients died. CONCLUSION: HIV-1-infected adults in Uganda are at high risk of pneumococcal disease and show a significant but suboptimal response to pneumococcal vaccine. Although reliable recruitment and follow-up of vaccinees is feasible, evaluation of vaccine efficacy may be compromised by limited responses to common vaccine serotypes, an unknown incidence of disease with non-vaccine serotypes, and a high rate of mortality unrelated to Streptococcus pneumoniae infection.

AIDS-Related Opportunistic Infections↗

Vaccine coverage with hepatitis B and other vaccines in the Colombian Amazon: do health worker knowledge and perception influence coverage?

OBJECTIVES: We conducted a vaccination coverage survey in the Colombian Amazon, an area highly endemic for hepatitis B (HB), where HB vaccine was introduced in 1992. The aim was to measure vaccine coverage and factors influencing it, especially those related to health services. METHODS: A total of 3573 children younger than 11 years were randomly selected from four populations. Vaccination status was ascertained through the vaccination card and a questionnaire on socio-demographic factors was applied to children's caretakers. Health workers (HW) in charge of vaccination in rural and urban areas were interviewed regarding knowledge and practices in vaccination. Individual and HW characteristics were related to individual vaccination using logistic regression. RESULTS: Overall cumulated vaccination coverage was high for polio (96%, 95% CI: 94-98), measles (94%, 95% CI: 92.8-95.2), BCG (91%, 95% CI: 90-93), DPT (90%, 95% CI: 88-92) and HB (88%, 95% CI: 86-90). However, <50% of children completed the primary course of vaccination in the first year of life. Individual factors improving the likelihood of being either fully or HB vaccinated were: age>1 year, living in Leticia, being affiliated to the social security, and living in a house with a roof made of tiles rather than palm tree leaf. Among the variables related to HWs, poor knowledge of vaccine contraindications predicted a lower chance of being fully or HB vaccinated in the population served by them, even after controlling for individual variables. CONCLUSIONS: The HB control program in Colombia has achieved good coverage in one of the most endemic areas of the country. However, barriers to vaccination arise from inequities in the distribution of health insurance and inadequate HW knowledge.

Attitude of Health Personnel↗

Patient compliance in the use of Vivotif Berna(R) vaccine, typhoid vaccine, live oral Ty21a.

BACKGROUND: Several live attenuated vaccines against bacterial enteric pathogens have recently been licensed. These include the Salmonella typhi Ty21a typhoid vaccine (Vivotif Berna(R) Vaccine) and Vibrio cholerae CVD103-HgR cholera vaccine (Mutacol Berna(R) Vaccine). They comprise a unique class of biologics in which patient compliance is required for their optimal use. This is of particular importance in the case of the Ty21a vaccine strain of which multiple doses are required. Furthermore, exposure to heat, concomitant use with antibiotics or antimalarial drugs, and timing of vaccination with respect to food intake can affect vaccine potency and/or efficacy. This study was conducted to determine the level of compliance among adult North American travelers and to evaluate compliance errors with respect to potential vaccine efficacy. METHOD: Questionnaires were provided to 1091 travelers at twelve travel clinics in the United States and Canada. The patients were requested to complete forms which asked questions relating to vaccine storage and usage, and to return them to the travel clinic. A total of 762 completed questionnaires were returned. RESULTS: Few compliance errors were made regarding proper storage of the vaccine. The most common compliance errors involved not taking all four capsules on alternate days (10%) and not taking all four doses of vaccine prior to departure (6%). CONCLUSIONS: Pretravel counselling was effective in obtaining a high compliance rate among adult travelers in the use of Vivotif Berna(R) Vaccine. The majority of compliance errors reported would not be expected to negatively impact upon vaccine efficacy.

Administration, Oral↗

Zonal-centrifuged purified duck embryo cell culture rabies vaccine for human vaccination.

Rabies virus produced in duck embryo cell culture was concentrated from volumes of 14 to 30 liters to 400 to 800 ml by zonal centrifugation. Virus titers of peak fractions were from 100- to 1,000-fold greater than those of the starting material. Vaccines were prepared by combining fractions with peak virus titers and diluting back to 10 times concentration. The resulting beta-propiolactone-inactivated vaccines, when prepared as lyophilized vaccines with AlPO(4) adjuvant diluents, were low in protein nitrogen (0.01 mg/ml), and three of four lots passed the National Institutes of Health potency test when tested as equivalent to a standard 10% suspension of duck embryo or mouse brain tissue vaccine. These vaccines also induced good sero-conversion in adult rabbits after a single 1-ml dose of vaccine. Guinea pigs sensitized with zonal-centrifuged purified duck embryo vaccine (with AlPO(4) adjuvant) did not exhibit anaphylactic shock reactions when challenged with homologous vaccine. Also, no anaphylactic shock reactions were observed when guinea pigs were sensitized with either a 10% experimental duck embryo vaccine or cell culture vaccine and then challenged with the zonal-purified vaccine. However, guinea pigs sensitized with cell culture or zonal-purified vaccine and then challenged with the 10% experimental vaccine did show slight transitory congestion. The 10% experimental whole duck embryo vaccine was responsible for all observed anaphylactic shock reactions whether homologous or heterologous.

Adjuvants, Immunologic↗

Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine.

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (> or =4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were cross-reactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

Amino Acid Sequence↗