The relationship between the immunological efficacy of a dried meningococcal group-A polysaccharide vaccine and the molecular parameters of the group-A polysaccharide

This work deals with the problem of relationship between the molecular parameters of group A meningococcal polysaccharide and its immunological effectiveness for laboratory animals and humans. The depolymerization of group A polysaccharide contained in the vaccine leads to a decrease in its capacity of inducing the production of hemagglutinating (19S and 7S) and bactericidal IgA antibodies in humans, as well as inducing an increase in the number of cells producing IgA antibodies in the spleen of immunized mice and the appearance of circulating IgA antibodies in their sera. As shown in this investigation, fully developed immune response to group A meningococcal vaccine may be achieved in humans only if the content of group A high-molecular polysaccharide in the vaccine is not less than 70%. Mice have been recommended as an experimental model for the prognostication of the effectiveness of meningococcal polysaccharide vaccines and for their control in the process of manufacture instead of currently used titration of bacteriolysins in the sera of immunized humans.     

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.     

Reactogenicity and immunogenicity of a new live attenuated combined measles, mumps and rubella vaccine in healthy children

Fas-mediated apoptosis is essential for the elimination of cells, and impaired apoptosis can have severe detrimental consequences. Bisindolylmaleimide VIII potentiated Fas-mediated apoptosis in human astrocytoma 1321N1 cells and in Molt-4T cells, both of which were devoid of apoptosis induced by anti-Fas antibody in the absence of bisindolylmaleimide VIII, and in Jurkat and CEM-6 T cells, which showed slight and moderate apoptotic responses, respectively, to low levels of Fas stimulation. Potentiation of Fas-mediated apoptosis by bisindolylmaleimide VIII was selective for activated, rather than non-activated, T cells, and was Fas-dependent, as it was not observed in T cells from Fas-deficient lpr/lpr mice. Administration of bisindolylmaleimide VIII to rats during autoantigen stimulation prevented the development of symptoms of T cell-mediated autoimmune diseases in two models, the Lewis rat model of experimental allergic encephalitis and the Lewis adjuvant arthritis model. Thus, the use of agents such as bisindolylmaleimide VIII may be therapeutically useful for supporting more effective elimination of detrimental cells through enhancement of Fas-dependent apoptosis signaling.     

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.     

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in children

We describe the incidence of respiratory viruses identified in children admitted to an Edinburgh hospital between October 1985 and July 1994. Respiratory syncytial (RS) virus, influenza viruses and parainfluenza viruses showed seasonal activity whereas adenoviruses and rhinoviruses did not. Parainfluenza viruses were the most changeable in their epidemiological behaviour and RS virus the least.     

Safety and immunogenicity of a new influenza vaccine grown in mammalian cell culture

In a phase I safety and immunogenicity study, 112 healthy adult volunteers were randomly allocated to receive a new bivalent (A/Texas/36/91[H1N1-like], B/Harbin/7/94) split virion influenza vaccine propagated in Madin-Darby Canine Kidney cell culture or an identical vaccine manufactured using currently licensed egg propagated virus technology. Soreness at the injection site was common but generally mild (75% of the cell culture-derived vaccine group and 62.5% of the egg-derived vaccine group; p = not significant). General reactions were less common; headache was the most frequently reported adverse effect (26.8 and 30.4%, respectively; p = not significant). Geometric mean haemagglutination inhibition titres post-immunization against the A/Texas strain were 1012 reciprocal dilution in the cell culture-derived vaccine group and 790 in the egg-derived vaccine group; against the B/Harbin strain titres were 420 and 447, respectively (all comparisons, p = not significant). It is concluded that the cell culture-derived split virion influenza vaccine is safe and immunogenic in healthy adult volunteers.     

High immunogenicity and good tolerability of a new hepatitis A vaccine candidate

Immunogenicity and tolerability of a new formalin-inactivated, alum-adjuvanted whole virus vaccine against hepatitis A (VAQTA, MSD, West Point, USA) were evaluated by immunizing 52 healthy, anti-HAV negative volunteers with a 1 ml dose. A booster dose was given 6 months later. In these young adult vaccinees [27 males and 25 females, 19-34 (mean 26) years of age] VAQTA proved to be well tolerated and highly immunogenic. Two weeks after administration of one vaccine dose, all but one of the recipients (98%) had anti-HAV concentrations above the presumed minimum protective level of 10 IU l-1 with a geometric mean concentration (GMC) of 165 IU l-1. After 4 weeks, a 100% seroconversion rate could be demonstrated with a fourfold increase of the GMC to 728 IU l-1. Six months after vaccination, all but one of the 50 volunteers coming back for booster (98%) showed anti-HAV levels within the protective range. The antibody concentrations had decreased in the majority of vaccinees to a GMC of 362 IU l-1. The booster dose given at that time was shown to be very effective, leading to a pronounced rise of anti-HAV levels in all recipients with a 17-fold increase of the GMC to 6040 IU l-1. Six months after the booster, all vaccinees were still seropositive with a GMC of 3444 IU l-1. Higher antibody levels were found in females, the difference being significant 4 weeks and 6 months after vaccination and 4 weeks after booster. No serious local or systemic adverse reactions were observed.     

Projective and identificatory illnesses among ex-hunter-gatherers: a seven-year survey of a remote Australian aboriginal community

THIS article attempts to provide answers from a psychiatric viewpoint to the question posed by Tindale (1974) in the opening paragraph of his Aboriginal Tribes of Australia: "What happens when a few small groups of people of family size are wresting a living from a given area of land by searching for food, over whose presence or growth they have no direct control?" Such very small-scale societies were a necessity in the Australian environment, where the Aboriginals were obliged to live by hunting and gathering. Indeed, the life-style of all manking was similar to this through most of the time span of human existence. The survey on which this article is based examined a community not long removed from that life-style, and found the defense mechanisms of projection and identification, which apparently persist because of their ancient function in assisting the adjustment of the individual and the group in these very small-scale societies. Some clans in this area have been in continuous contact with whites for only 25 years, and the others for about 60 years, so it is unlikely that the modal defenses of the people have changed. The child-rearing patterns that contributed to the defenses, appropriate to a society organized into clans, probably also have not changed significantly. Intensified by stresses of modern origin, these defenses shape the psychiatric illnesses of today.     

Household and community determinants of exposure to involuntary smoking: a study of urinary cotinine in children and adolescents

The study examines the role of several potential predictors of urinary cotinine levels in a cross-sectional sample of 1,072 nonsmoking children and adolescents in Latium, Italy, during 1990-1991. As expected, there was a strong relation between passive exposure to smoking and the amount of maternal and paternal self-reported smoking. The urinary cotinine level increased with a decreasing level of paternal education and with an increasing index of household crowding; self-report of recent exposure to smoking outside the home was a strong predictor of the biologic marker. The analysis was then restricted to 346 subjects whose parents claimed that they were nonsmokers and that there were no smokers at home. In this group, however, 57 children reported some active smoking at home by their parents. Those with parents suspected to be "deceivers" had higher level of urinary cotinine than did those truly not exposed. In addition, urinary cotinine in this group was clearly associated with duration of exposure to smoking outside home. The study indicates that both factors related to family circumstances and exposure outside the household setting are strong determinants of urinary cotinine levels. The finding may be considered a direct confirmation that passive smoking among children should be viewed as a specific community responsibility.     

Follow-up immunogenicity of an inactivated hepatitis A virus vaccine in healthy children: results after 5 years

Long-term persistence of hepatitis A virus (HAV) serum antibody in vaccinated children has not been demonstrated in previous studies. To study the long-term immunogenicity to HAV vaccine, three doses of strain HM 175 HAV vaccine with 360 enzyme-linked immunosorbent assay units were administered to 107 children, aged from 1.0 to 6.8 years, at 0, 1, and 6 months. The administration of one vaccine dose induced seropositivity (anti-HAV titer > or = 20 mIU ml-1) in 95% of all vaccinees at month 1. All subjects remained seropositive until month 6. The titers of HAV antibody remained above 20 mIU ml-1 in all subjects followed up to 60 months. The geometric mean titer (GMT) reached its peak (3802 mIU ml-1) at month 7, i.e. 1 month after the booster dose, and then declined until the end of follow-up at month 60 (661 mIU ml-1). A trend of higher GMT in female subjects persisted up to month 60. The changes of the GMT over time were best described by the regression equation: log (GMT) = 3.26-0.08 x (age in years) (r = -0.95, P = 0.014). According to this equation, the geometric mean concentration would reach 20 mIU ml-1 at around 24.5 years after the beginning of vaccination. In conclusion, those who completed the recommended three-dose inactivated HAV vaccination series remained seroprotective for at least 5 years. Theoretically, such a vaccination program can provide a protective period of over 20 years in children. This paper may be the first to describe at least 5-year immunogenicity of inactivated HAV vaccination in healthy children.     

Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults

The adjuvanted influenza vaccine FLUAD is composed of subunit influenza antigens combined with the MF59-adjuvant emulsion. The vaccine was developed primarily for use in elderly populations, but non-elderly individuals might also benefit. To evaluate this hypothesis, 301 healthy adults were assigned randomly to receive two intramuscular injections of either FLUAD (150 subjects) or a non-adjuvanted vaccine, Fluzone (151 subjects), in two trials conducted at a 1-year interval. Injections consisted of 15 micrograms per 0.5 ml dose. Vaccine composition was A/Texas/36/91 (H1N1), A/Johannesburg/33/94 (H3N2), and B/Harbin/7/94 for the first injection and A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2), and B/Harbin/7/94 for the second injection. Immunogenicity was evaluated at 28 and 180 days post-immunization. FLUAD was generally well tolerated in healthy adults when compared with Fluzone. FLUAD was associated with increased pain at the injection site after immunization. A statistically significant increase in the incidence of injection-site warmth, chills, myalgia, and analgesic/antipyretic use occurred in the FLUAD group after the first injection but not after the second injection. In both groups, most of these local and systemic reactions were classified as mild. FLUAD was more immunogenic than Fluzone following both injections. After the first injection, statistically significant differences were found in the percentage of subjects with four-fold rises in hemagglutinin inhibition (HI) titers at 28 days post-immunization for the B antigen. After the second injection, the FLUAD group had significantly higher HI titers, a significantly higher percentage with a four-fold increase in titer, and a significantly greater percentage of subjects with titers >/=160 for the H3N2 antigen at 28 days. Only minor immunogenicity differences between the two groups were seen at 180 days. Compared with Fluzone, FLUAD was associated with increased immunogenicity and mild post-immunization reactions in healthy adults. The magnitude of increased immunogenicity in healthy adults was less than that seen in elderly populations.     

Low dietary fiber and high protein intakes associated with newly diagnosed diabetes in a remote aboriginal community

The high prevalence of diabetes mellitus in North American aboriginal populations may be due to recent changes in lifestyle, including the adoption of a high-fat, low-fiber diet. To determine whether fat or fiber intakes were associated with new cases of diabetes, we studied 72% (728/1018) of residents aged > 9 y from a remote aboriginal community in northern Ontario using the 75-g oral-glucose-tolerance test and 24-h dietary recall. The mean fat intake of this population (36% of energy) was typical for North America, but fiber intake (1.2 g/MJ) was very low. Logistic-regression analysis, adjusted for age, sex, and body mass index, showed that a 1-SD increase in fiber intake reduced the risk of having diabetes by 39% (P = 0.026) whereas the same increase in protein intake increased the risk by 38% (P = 0.027). There was no significant effect of energy, fat, starch, or simple sugars. These data support Trowell's original dietary-fiber hypothesis that "... dietary fiber depleted starchy foods are conducive to the development of diabetes mellitus in susceptible human genotypes."     

Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents

BACKGROUND: The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents. Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old, the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group. MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days postvaccination using diary cards. Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components. RESULTS: Both vaccines showed good tolerability, local and general reactogenicity being similar. For local reactions Group 1=88.1% and Group 2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV. The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune responses were obtained against all vaccine components. CONCLUSIONS: The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents. To prevent recent resurgence of pertussis in France, this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France.     

Estimates of food and macronutrient intake in a random sample of Northern Ireland adolescents

Estimates of food consumption and macronutrient intake were obtained from a randomly selected population sample (2%) of 1015 adolescents aged 12 and 15 years in Northern Ireland during the 1990/1991 school year. Dietary intake was assessed by diet history with photographic album to estimate portion size. Reported median energy intakes were 11.0 and 13.1 MJ/d for boys aged 12 and 15 years respectively and 9.2 and 9.1 MJ/d for girls of these ages. Protein, carbohydrate and total sugars intakes as a percentage of total energy varied little between the age and sex groups and were approximately 11, 49 and 20% respectively of daily total energy intakes. Median dietary fibre intakes were approximately 20 and 24 g/d for boys aged 12 and 15 years respectively and 18 and 19 g/d for girls of these ages. Major food sources of energy (as a percentage of total energy intakes) were bread and cereals (15-18%), cakes and biscuits (12-14%), chips and crisps (13-14%), dairy products (9-11%), meat and meat products (9-11%) and confectionery (9%). Fruit and vegetable intakes were low at about 2.5% and 1.5% respectively of total energy intakes. Median fat intakes were high at 39% of total daily energy intakes. Major food sources of fat as a percentage of total fat intakes were from the food groupings: chips and crisps (16-19%), meat and meat products (14-17%), fats and oils (14-16%), cakes and biscuits (13-16%) and dairy products (12-15%). Median intakes of saturated fatty acids were also high at approximately 15% of daily total energy intake while intakes of monounsaturated fatty acids averaged 12% of daily total energy intake. Median polyunsaturated fatty acid (PUFA) intakes were low, comprising 5.2 and 5.5% of daily total energy intake for boys aged 12 and 15 years respectively and were lower than the PUFA intakes (5.9 and 6.3% of daily total energy intake) for girls of these ages. About 1.3% for boys and 1.4% for girls of daily total energy intake was in the form of n-3 PUFA. Ca and Mg intakes were adequate for both sexes. Based on these results, some concern about the dietary habits and related health consequences in Northern Ireland adolescents appears justified.     

Seroepidemiology of emerging tickborne infectious diseases in a Northern California community

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51(23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11-20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.     

The effectiveness of a tobacco prevention program with adolescents living in a tobacco-producing region

OBJECTIVES: This study investigated the efficacy of a social-influences tobacco prevention program conducted with adolescents living in a high tobacco production area. METHODS: Students in 10 experimental schools completed the tobacco prevention program and a booster intervention. Control students received health education as usual. RESULTS: After 2 years of treatment, smoking rates in the treatment group (vs the control group) were lower for 30-day, 7-day, and 24-hour smoking. The intervention had more of an impact on those who were involved in raising tobacco than it did on those not involved in raising tobacco. CONCLUSIONS: Although modest, effects were achieved with minimal intervention time in a high-risk group, indicating that social-influences prevention programs may be effective in such groups.     

Safety and immunogenicity of Brucella abortus strain RB51 vaccine in pregnant cattle

L-Asparaginase derived from Erwinia chrysanthemi which is being investigated as an alternative to E. coli for the treatment of lymphoblastic leukaemia has been found in our laboratory to lose activity upon exposure to consecutive freeze-thaw cycles. An investigation was undertaken using several techniques to characterize fully the physicochemical changes L-Asparaginase is undergoing during freeze-thaw cycling leading to the loss of its activity. A total protein assay suggested that the loss of some enzyme activity was a result of protein precipitation. Circular dichroism (CD) studies showed a decrease of alpha-helical structure with a concomitant increase in beta sheet and random coil content, suggesting alterations in the secondary structure leading to unfolding, the first step of denaturation processes. The elution profiles obtained from size-exclusion chromatography (SEC) studies indicated the formation of several species during the process of freezing and thawing. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) studies showed bands corresponding to 1-3 kDa and 32 kDa, suggesting that some of the species are fragments and shortened monomers resulting from cleavage of monomers. The molecular weight distribution obtained using SEC-linked light scattering indicated a substantial fraction of polydispersed fragments ranging from 900 Da to 3 kDa and a small fraction of aggregates corresponding to 300 kDa. A scheme was proposed to explain the cascade of events leading to the loss of soluble protein and accompanying loss of enzyme activity. Tetramers of the enzyme dissociate into monomers some of which are cleaved into small fragments. The shortened monomers then aggregate and precipitate.