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PubMed1997

[Immunologic behavior of meningococcal vaccines].

Meningococcal disease continues to be a great health problem on all continents and the meningococcal vaccines have been proposed for their prevention and epidemic control. The polysaccharide A and C vaccines are relatively efficacious with distinct immunological behavior with regard to the different age groups, however, up to the present no highly efficacious vaccine for meningococcal B disease exists. The meningococcal B capsular polysaccharide is not immunogenic due to the structural mimicry of mammalian tissues and efforts to produce carrier proteins have been proposed in order to obtain an immunogenic vaccine for all age groups that would if possible, protect against all the meningococci. This review of the literature presents the study of the development of the immunological behavior of all the meningococcal vaccines undergoing development and reports on the efforts to obtain a safe and efficacious product for the control of meningococcal disease.

Bacterial Vaccines↗
PubMedDate not supplied

Crossover vaccination with quadrivalent meningococcal vaccine (against A/C/Y/W-135) following recent application of bivalent meningococcal vaccine (against A/C): assessment of safety and side effect profile.

BACKGROUND: Until May 2000, bivalent A/C meningococcal vaccine was the only available vaccine in Singapore for hajj travelers to Saudi Arabia. Recent worldwide reports of serogroup W-135 meningococcal meningitis associated with hajj returnees necessitated switching to quadrivalent A/C/Y/W-135 vaccine and crossover vaccination of travelers to Saudi Arabia. No safety data are available for quadrivalent vaccine following recent vaccination with bivalent vaccine. We assessed the safety and side effect profile of bivalent, quadrivalent, and quadrivalent meningococcal vaccine after recent vaccination with bivalent vaccine. METHODS: A postvaccination telephone questionnaire survey was performed for all travelers who received either bivalent (B), quadrivalent (Q), or quadrivalent with recent (as defined by less than 6 months before) bivalent meningococcal vaccine (BQ) between 22 May and 8 June 2000 in preparation for the umrah (minor pilgrimage). Patients were asked about local reactions (pain, erythema, swelling at injection site graded in mild, moderate, and severe) and systemic reactions (fever, headache, graded in mild and severe). RESULTS: Of 546 persons vaccinated, 323 were interviewed. Median time interval between interview and vaccination was 10 days. Of those interviewed, 64 patients received bivalent (B), 213 quadrivalent (Q), and 46 quadrivalent after recent bivalent vaccine (BQ). The median interval time between previous bivalent and quadrivalent vaccine was 5 weeks. There was no statistically significant difference in the prevalence of side effects between the three groups. Mild pain at injection site was recorded in B as 21.8%, Q as 23%, BQ as 21.7%; low grade fever in B as 7.8%, Q as 9.8%, and BQ as 15.2%. CONCLUSIONS: Bivalent and quadrivalent meningococcal vaccine are well tolerated. Crossover vaccination of quadrivalent meningococcal vaccine after recent vaccination with bivalent vaccine does not increase the prevalence of adverse reactions and is therefore safe.

Adolescent↗
PubMed2004

Meningococcal vaccines.

Meningococcal disease is one of the most feared and serious infections in the young and its prevention by vaccination is an important goal. The high degree of antigenic variability of the organism makes the meningococcus a challenging target for vaccine prevention. Meningococcal polysaccharide vaccines against serogroup A and C are efficacious and have been widely used, often in combination with serogroup Y and W135 components. Their relative lack of immunogenicity in young children and infants can be overcome by conjugation to a protein carrier. The effectiveness of serogroup C glycoconjugate vaccines in children of all ages has been demonstrated and they have now been introduced into routine vaccination schedules. Conjugate vaccines against other serogroups, including A, Y, and W135 will soon be available and it is hoped they may emulate this success. Prevention of serogroup B disease has proven more elusive. Several serogroup B vaccines based on outer membrane vesicles have been shown to be immunogenic and reasonably effective in adults and older children, but the protection offered by them is chiefly strain-specific. Multivalent recombinant PorA vaccines have been developed to broaden the protective effect, but no efficacy data are available as yet. Intensive efforts have been directed at other outer membrane protein vaccine candidates and lipopolysaccharide, and some of these have been shown to offer protection in experimental animal models. Nonpathogenic Neisseriae spp. such as Neisseria lactamica are also possible vaccine candidates. Previously unknown proteins have been identified from in silico analysis of the meningococcal genome and their vaccine potential explored. However, none of these has yet been presented as the 'universal' protective antigen and work in this field continues to be held back by our limited knowledge concerning the mechanisms of natural protection against serogroup B meningococci.

Adolescent↗
PubMed1996

[Polysaccharide vaccines. II. Meningococcal vaccines].

A short history of vaccination and troubles connected with preparation of vaccine effective in preventing serogroup B meningococcal diseases was described. Different kinds of meningococcal vaccines used all over the world and epidemiological situation in Poland was also discussed.

Child, Preschool↗
PubMed2004

[Acceptance of the new conjugate vaccines. Meningococcal and pneumococcal vaccines, in the cohort born in 1999, in the North Region of Portugal].

The new conjugate vaccines against group C meningococcal infection and pneumococcal infection were introduced in Portugal in 2001. In 2001/2002, the media published several alarming news on meningococcal disease and there was an increased demand of those vaccines, not included in the Portuguese National Vaccination Programme. In order to assess the coverage with these new vaccines against Neisseria meningitidis and Streptococcus pneumoniae, we conducted a descriptive study of the cohort born in 1999, using a convenience sample, from eight health centres in the North of Portugal. Data was collected from the vaccination records of 1877 children born in 1999: 37.2% had received the group C meningococcal conjugate vaccine and 33.3% the pneumococcal conjugate vaccine, while 21,2% had received both. Most vaccinations with pneumococcal conjugate vaccine were performed after 23 months of age, above the recommended age range. The biggest number of group C meningococcal conjugate vaccines given in a month, was recorded in February of 2002, when the maximum number of reported cases of meningococcal disease was also observed. Correlation of both distributions over time was very high (R(2)=0.95). In February 2002 the number of pneumococcal conjugate vaccine doses given rose again, after having been decreasing since October 2001. This study suggested research hypothesis for the future.

Child, Preschool↗
PubMed2005

[Investigation concerning demand and vaccination applicants to traveler's vaccines (typhoid fever and meningococcal vaccines) not marketed in Japan].

In recent years, the number of Japanese traveling to foreign countries is increasing. Most of them travel to Asian regions where many infectious diseases that are rare or don't occur in Japan still remain endemic or epidemic. Of these infectious diseases typhoid fever and meningococcal infection are now preventable because safe and effective vaccines have been developed and now marketed. However, these vaccines are hardly available in Japan because the Japanese Government has not admitted them. To investigate the demand for the two vaccines, the author personally imported inactivated polysaccharide typhoid vaccine and groups A, C,Y and W135 combined polysaccharide meningococcal vaccine, both manufactured by Aventis-Pasteur. After obtaining approval of the ethical committee of our hospital, vaccination was started. From May 6, 2003 to September 30, 2004, 124 applicants received typhoid vaccine and 35 were injected with meningococcal vaccine. Of 124 vaccinees of typhoid vaccine, 46 went to Afghanistan, 15 to India, 8 to Thailand. Of 35 vaccinees of meningococcal vaccine 6 went to the USA, 5 to Guinea and 3 to England. In addition a total of 12 physicians and nurses having no international scheduled trip were also immunized with meningococcal vaccine. None of these vaccines are widely known in Japan now. Based on our results, however, the expansion of recognition and demand for these two vaccines is expected.

Adult↗
PubMed2002

Meningococcal vaccine use in college students.

OBJECTIVE: To discuss the role of meningococcal vaccine in prevention of meningococcal disease. DATA SOURCES: A MEDLINE search (1966-June 2001) was performed to identify key literature. Search terms included, but were not limited to, meningococcal vaccines, meningococcal meningitis, meningococcal infection, and meningococcus. The search was limited to English-language literature and references dealing with humans. The MEDLINE search was supplemented by a hand search of various bibliographies. DATA SYNTHESIS: The impact of meningococcal disease has caused national and regional organizations to develop recommendations for use of meningococcal vaccine. Even though the meningococcal vaccine can provide benefit, limitations exist. The available vaccine does not cover all meningococcal strains and is not useful in all age groups. The appropriate target groups for prevention of disease through vaccination have been difficult to determine; vaccine use in college students is especially controversial. CONCLUSIONS: Although a meningococcal vaccine is available, meningococcus causes significant morbidity and mortality. Controversy exists over the meningococcal vaccine and its use. Students entering college who will be living in dormitories should be informed of the increased risk of meningococcal disease and be offered vaccination.

Adult↗
PubMed2005

Evidence of positive Darwinian selection in putative meningococcal vaccine antigens.

Meningococcal meningitidis is a life-threatening disease. In Europe and the United States the majority of cases are caused by virulent meningococcal strains belonging to serogroup B. Presently there is no effective vaccine against serogroup B strains, as traditional vaccine antigens such as polysaccharide capsules are unusable as they lead to autoimmunity. The year 2000 saw the publication of the complete genome of Neisseria meningitidis MC58, a virulent serogroup B bacterium. Working in conjunction with the sequencing project, researchers endeavored to locate highly conserved membrane-associated proteins that elicit an immune response. It is hoped that these proteins will provide a basis for novel vaccines against serogroup B strains. A number of potential vaccine antigens have been located and are presently in phase I clinical trials. Recently many reports pertaining to the evidence of positive Darwinian selection in membrane proteins of pathogens have been reported. This study utilized in silico methods to test for evidence of historical positive Darwinian selection in seven such vaccine candidates. We found that two of these proteins show signatures of adaptive evolution, while the remaining proteins show evidence of strong purifying selection. This has significant implications for the design of a vaccine against serogroup B strains, as it has been shown that vaccines that target epitopes that are under strong purifying selection are better than those that target variable epitopes.

Amino Acid Sequence↗
PubMed2006

Optimization of the conjugation method for a serogroup B/C meningococcal vaccine.

A conjugate meningococcal vaccine against serogroup B/C consisting of capsular PS (polysaccharide) from serogroup C conjugated to OMV (outer membrane vesicle) from serogroup B would be a very useful vaccine in regions where there is a prevalence of both serogroups, for example in Brazil. For this purpose, the conjugation method that uses ADHy (adipic acid dihydrazide) as spacer and a carbodi-imide derivative, EDAC [1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide], as catalyser was optimized looking for synthesis yield and maintenance of the antigenicity of both components. The best synthesis conditions preserving the vaccine immunogenicity resulted in a final yield of approx. 17%. Immunogenicity of the vaccine was highest when 10% of the sialic acid residues of the PS were occupied by the ADHy spacer. Sterilization of the conjugate by filtration through a 0.22-microm-pore-size membrane resulted in a low recovery of protein and PS (approximately 50%), although the vaccine immunogenicity was maintained. Using gamma irradiation on freeze-dried sample, it was possible to maintain the integrity of OMV structure and, consequently, its ability to induce bactericidal antibodies.

Adipates↗
PubMed1998

Efficacy of meningococcal vaccine and barriers to vaccination.

CONTEXT: Use of the quadrivalent meningococcal vaccine for control of outbreaks has increased in recent years, but the efficacy of meningococcal vaccine during mass vaccination campaigns in US civilian populations has not been assessed. OBJECTIVES: To evaluate the efficacy of the quadrivalent meningococcal vaccine against serogroup C meningococcal disease in a community outbreak setting and to evaluate potentially modifiable barriers to vaccination in an area with persistent meningococcal disease following immunization. DESIGN: Matched case-control study of vaccine efficacy using cases of serogroup C meningococcal disease in persons eligible for vaccination during mass vaccination campaigns. Control patients were matched by neighborhood and age. The control group was used to identify possible barriers to vaccination. SETTING: Gregg County, Texas, population 106076, from 1993 to 1995. PARTICIPANTS: A total of 17 case patients with serogroup C meningococcal disease eligible for vaccine and 84 control patients. MAIN OUTCOME MEASURES: Vaccine efficacy and risk factors associated with nonvaccination. RESULTS: Vaccine efficacy among 2- to 29-year-olds was 85% (95% confidence interval, 27%-97%) and did not change in bivariate analyses with other risk factors that were significant in univariate analysis. Among control patients, older age was strongly associated with nonvaccination; vaccination rates for 2- to 4-year-olds, 5- to 18-year-olds, and 19- to 29-year-olds were 67%, 48%, and 20%, respectively (chi2 for linear trend, P=.01). CONCLUSIONS: The meningococcal polysaccharide vaccine was effective against serogroup C meningococcal disease in this community outbreak. Although specific barriers to vaccination were not identified, older age was a risk factor for nonvaccination in the target population of 2- to 29-year-olds. In future outbreaks, emphasis should be placed on achieving high vaccination coverage, with special efforts to vaccinate young adults.

Adolescent↗
PubMed2005

Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients.

Two peaks in the incidence of invasive meningococcal disease (IMD) occur in pediatric patients: infants younger than 1 year and adolescents 15 to 18 years of age. Although the incidence of IMD is highest in infants, the case-fatality rate is highest in adolescents (approximately 20%). Epidemiologic studies also have demonstrated increased risk of IMD among college freshman living in dormitories compared with other college students and similarly aged persons in the general population. At least 75% of cases of IMD in 11- to 18-year-olds are caused by serogroups A, C, Y, and W-135; thus, IMD potentially is preventable by immunization with quadrivalent meningococcal vaccines. Meningococcal A, C, Y, W-135 conjugate vaccine (MCV4) was licensed in 2005 for use in people 11 to 55 years of age. On the basis of data indicating increased risk of meningococcal disease and fatality among certain adolescents and college students, the American Academy of Pediatrics recommends administration of MCV4 to young adolescents (at the 11- to 12-year visit), students entering high school or 15-year-olds, and college freshmen who will be living in dormitories. For pediatric patients 11 years and older who are at increased risk of meningococcal disease, MCV4 also is recommended. The purposes of this statement are to provide the rationale for routine use of MCV4 in adolescents and to update recommendations for use of the meningococcal polysaccharide vaccine in pediatric patients.

Adolescent↗
PubMed2000

Predictors of vaccination rates during a mass meningococcal vaccination program on a college campus.

Factors contributing to students' compliance with mass vaccination programs during meningococcal outbreaks have not been well described. A 1997 mass vaccination campaign at Michigan State University provided an opportunity to study such factors. Of 34,024 students in the target population, 17,538 (51.5%) were vaccinated in 5 days. Vaccination rates were higher for women (47.9%) than for men (43.1%) and higher for on-campus residents (65.3%) than for off-campus residents (35.6%). For each year of students' age beyond 19, the adjusted odds of vaccination were reduced by 0.82. Adjusted odds ratios for vaccination, with White students as the reference group at 1.0, were 1.33 for Asian American students, 0.97 (not significant) for Hispanic students, 0.82 for African American students, and 0.80 for Native American students. Students from the Colleges of Business, Engineering, Communication, and Natural Science had the highest vaccination rates; those from the College of Arts and Letters had the lowest rates.

Adult↗
PubMed2000

Phagocytic killing and antibody response during the first year after tetravalent meningococcal vaccine in complement-deficient and in normal individuals.

Seven individuals with late complement component (LCC) deficiency and seven control subjects were vaccinated with tetravalent meningococcal vaccine. The response to vaccination was evaluated by measuring the antibody titer and the phagocyte killing of the bacteria, before, 5-7 weeks, and 12-14 months after vaccination. Prior to vaccination, no phagocytic killing and a low titer of antibody was found in the LCC-deficient group and a low killing (mean of 40-58%, according to the serogroup) in normal controls. The phagocytic killing increased significantly 5-7 weeks after vaccination. However, while in normal controls the phagocytic killing was close to 100% after 5-7 weeks and decreased only slightly during the first year, the mean killing of the various meningococcal subgroups in LCC-deficient individuals was 70-89% and dropped to only 53-71% one year after vaccination. Six weeks after vaccination the mean antimeningococcal antibody titer increased similarly in the sera of LCC-deficient patients and controls. One year after vaccination the controls maintained the high concentration, while the LCC-deficient patients had tendency toward a decrease. In addition, the interpersonal variability of the antibody concentration, both in LCC-deficient individuals and in normal controls, was much higher than the phagocytic killing, with only a very mild increase in some individuals. Thus, it is possible that in spite of adequate increase of antimeningococcal antibody titer after vaccination of LCC-deficient individuals their immunity against the bacteria may not be optimal. Our data show also that phagocytic killing of meningococci is probably a more consistent assay than antibody titer levels for antimeningococcal immunity, especially in LCC-deficient patients.

Antibodies, Bacterial↗
PubMed1996

Adverse events temporally associated with meningococcal vaccines.

OBJECTIVE: To determine the incidence of severe adverse events temporally associated with meningococcal vaccines administered as part of a mass vaccination program. DESIGN: Retrospective descriptive study of events reported to a passive provincial surveillance system. SETTING: The province of Quebec. PARTICIPANTS: The 1,198,751 individuals aged 6 months to 20 years who were vaccinated against meningococcal disease between Dec. 27, 1992, and Mar. 31, 1993. OUTCOME MEASURES: Total numbers and rates of severe adverse events, including allergic reactions, anaphylactic reactions, neurological events (other than abnormal crying and screaming) and other serious or unusual events. RESULTS: A total of 118 reports of severe adverse events were selected from the surveillance system. The most frequent were allergic reactions (9.2 per 100,000 doses). Few anaphylactic or neurologic reactions were reported (0.1 and 0.5 per 100,000 doses respectively). There were no reports of sequelae or of encephalopathy, meningitis or encephalitis. CONCLUSION: Meningococcal vaccines seem to be associated with fewer adverse events than have previously been reported. Existing surveillance programs are useful for determining the incidence of adverse events temporally associated with vaccines.

Adolescent↗
PubMed1998

Opsonophagocytic and bactericidal activity mediated by purified IgG subclass antibodies after vaccination with the Norwegian group B meningococcal vaccine.

To study how the different immunoglobulin (Ig)G subclass antibodies may confer protection against systemic meningococcal disease, we isolated IgG1, IgG2 and IgG3 antibodies from plasma from vaccinees immunized with the Norwegian meningococcal outer membrane vesicle vaccine. Four IgG1, one IgG2 and four IgG3 preparations were purified. The IgG2 and IgG3 subclass preparations were free from contaminating subclasses, whereas the IgG1 preparations contained from 0 to 14% of IgG2 and/or IgG3. Immunoblotting against whole-cell meningococcal antigens showed broad specificities of the various preparations, both within and between subclasses. These subclass preparations were tested for opsonophagocytic and bactericidal activity. As targets we used two different variants of the meningococcal vaccine strain, with low (44/76-SL) and high (44/76-1) expression of the outer membrane protein Opc. Using polymorphonuclear leucocytes as effector cells in the presence of human complement, all three IgG subclass preparations revealed high, and similar, opsonophagocytic activities against 44/76-SL, whereas against 44/76-1 the IgG2 preparation showed a reduced activity and most IgG3 preparations were slightly more active than the IgG1 preparations. Regarding bactericidal activity, all the three subclasses were highly active against 44/76-SL. Against 44/76-1 the bactericidal activities were somewhat more varied: all IgG1 and three IgG3 preparations exhibited higher activities than against 44/76-SL. Due to the low concentration in the IgG2 preparations, only a weak activity was seen against 44/76-1. One IgG3 preparation that was highly opsonophagocytic revealed no bactericidal activity against either of the two bacterial variants examined. In conclusion, we have shown that the IgG subclass effector functions differ from person to person, but that antibodies of IgG1, IgG2 and IgG3 subclasses, judged by their behaviour in the functional tests, may all contribute to protection against meningococcal disease.

Antibody Specificity↗
PubMedDate not supplied

[Evolution of meningococcal infection among infant population in the autonomous community of Valencia (1996-2000). Effectiveness of A+C meningococcal vaccination].

BACKGROUND: The increase in meningococcal disease caused by serogroup C in the Autonomous Community of Valencia during the 1996-1997 period gave rise to an A + C meningococcal vaccination campaign having been conducted targeting the population ranging from 18 months to 19 years of age. The purpose of this study is that of analyzing the impact of this campaign regarding the epidemiology, clinical aspects and evolution of meningococcal disease and the vaccination status of the youth population for the purpose of evaluating the efficacy of this vaccination. METHODS: The data was taken from the clinical records of the children under 15 years of age who showed clinical signs and symptoms suggesting an invasive disease with isolation of Neisseria meningitidis and/or which meet the established case definition criteria which had been treated at all of the public hospital in the Autonomous Community of Valencia within the 1996-2000 period. The trend of incidence was evaluated by means of incidence rates. The clinical aspects and their progress (sequelae and lethality) by frequency and distribution by serogroup and age. The vaccination efficacy was calculated using the Orestein equation. RESULTS: A total of 302 cases of invasive disease caused by N. Meningitidis were recorded. The rate of incidence by serogroup C in children under age 15 dropped following the vaccination campaign from 5.82/10(5) habitants in 1997 to 1.68/10(5) habitants in 1998. Rates similar to those prior to the time prior to the vaccination recorded three years subsequent to the campaign, showing an increase in the disease caused by serogroup B over the last 2 years. Sixty-one percent of the sequelae were among children under 5 years of age. Lethality was higher for serogroup C. Vaccination efficacy three years subsequent to the campaign was 83.7% for the 5-14 age range and 69.1% for the 19 month-4 year age range. CONCLUSION: The polysaccharide vaccine was shown to be effective for halting the outbreak. The drop in the incidence of serogroup C can be attributed to the vaccination efficacy achieved.

Adolescent↗
PubMed2004

[Meningococcal vaccination: which one? When? Why?].

Two kinds of meningococcal vaccines are available for invasive meningococcal infections (IMI) prevention, non conjugated polysaccharide vaccines anti A+C or anti A+C+W135+Y and conjugated polysaccharide vaccines anti-C. The last one have the advantage of being effective from 2 months of age. Vaccination should to be used in four circumstances: for subjects remaining in close contact with an IMI case; for pilgrims going to Mecca (A+C+W135+Y vaccine must be used); for travelers to a location with active transmission of IMI and close contacts with local population; in case of "mass" vaccination decided by health authorities. Generalised vaccination of all of one or more age groups has been done for serotype C in some European countries, because of high incidence. Effectiveness of this kind of intervention should be weighted with the risk of immunoselection of another serotype and with the possibility of a spontaneous decrease of the incidence.

Age Factors↗