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Knowledge about vaccines and willingness to participate in preventive HIV vaccine trials: a population-based study, Rakai, Uganda.

The purpose of the study was to assess knowledge and beliefs regarding vaccines and willingness to participate in HIV vaccine trials. A baseline survey assessed knowledge and attitudes toward vaccination and potential HIV vaccines among 14,177 participants aged 15-49 years, in a population cohort. Willingness to participate in HIV-preventive vaccine trials was assessed during a follow-up survey 10 months later after providing community education on HIV vaccines. Knowledge of the preventive utility of vaccines was high (71%), but higher in men than women (P<0.001), and increased with education levels (P<0.001). Vaccines were considered appropriate for children and women (99 and 88%, respectively), but not for adult men (28%). Participants felt that adolescents were the most appropriate subjects for HIV preventive vaccine trials (93.7%) but also thought that HIV-positive persons were eligible for trials (60.2%), and only 20% thought a preventive vaccine could help control HIV. HIV vaccine awareness increased from 68% at baseline to 81% at follow-up (P<0.001). Willingness to participate in HIV-preventive vaccine trials was 77%. Vaccine knowledge and willingness to participate in trials are high in this population. However, there still is need for education on the potential role of preventive HIV vaccines in the control of the epidemic and the importance of vaccination for men, especially in the context of an HIV vaccine.

AIDS Vaccines↗

Varicella vaccine effectiveness during an outbreak in a partially vaccinated population in Spain.

BACKGROUND: An outbreak of varicella occurred between December 2004 and April 2005 in the primary school and day-care center of a town of 5430 inhabitants in Spain. Although the varicella vaccine is not included in the infant vaccination program, some children had been vaccinated before the outbreak. STUDY AIM: The aim of this study was to estimate varicella vaccine effectiveness during an outbreak that took place in a partially vaccinated population of children. METHODS: A cohort study was carried out. Cases were identified through notification by doctors and active search. Information was gathered on the current disease, history of varicella and previous vaccinations together with age, course, school year and other sociodemographic factors. The relative risk (RR) of varicella and the contribution of the previously mentioned factors to the probability of contracting the disease was estimated for vaccinated and unvaccinated children. RESULTS: Participation reached 96.5% (387 of 401 children) in the school and 91.2% (31 of 34 children) in the day-care center. Of 269 children with no history of varicella and with a documented vaccination record, 96 (35.7%) had been previously vaccinated. During the outbreak, 148 cases of varicella were observed. The overall attack rate was 54.4%, 22.9% in vaccinated and 72.8% in unvaccinated children. RR of varicella in vaccinated children was 0.31 (95% confidence interval [CI] = 0.21-0.46). The overall adjusted vaccine effectiveness against varicella was 69.5% (95% CI = 50.5-81.5%) and 96.9% (95% CI = 77.5-99.6%) against mild and severe forms. Only time since vaccination was associated with vaccine failure. CONCLUSIONS: In the varicella outbreak studied, we conclude that vaccine was effective in the prevention of the disease, particularly in its moderate and severe forms, but because the proportion of vaccinated children was low, an outbreak still occurred.

Age Factors↗

Identification and characterization of avian retroviruses in chicken embryo-derived yellow fever vaccines: investigation of transmission to vaccine recipients.

All currently licensed yellow fever (YF) vaccines are propagated in chicken embryos. Recent studies of chick cell-derived measles and mumps vaccines show evidence of two types of retrovirus particles, the endogenous avian retrovirus (EAV) and the endogenous avian leukosis virus (ALV-E), which originate from the chicken embryonic fibroblast substrates. In this study, we investigated substrate-derived avian retrovirus contamination in YF vaccines currently produced by three manufacturers (YF-vax [Connaught Laboratories], Stamaril [Aventis], and YF-FIOCRUZ [FIOCRUZ-Bio-Manguinhos]). Testing for reverse transcriptase (RT) activity was not possible because of assay inhibition. However, Western blot analysis of virus pellets with anti-ALV RT antiserum detected three distinct RT proteins in all vaccines, indicating that more than one source is responsible for the RTs present in the vaccines. PCR analysis of both chicken substrate DNA and particle-associated RNA from the YF vaccines showed no evidence of the long terminal repeat sequences of exogenous ALV subgroups A to D in any of the vaccines. In contrast, both ALV-E and EAV particle-associated RNA were detected at equivalent titers in each vaccine by RT-PCR. Quantitative real-time RT-PCR revealed 61,600, 348,000, and 1,665,000 ALV-E RNA copies per dose of Stamaril, YF-FIOCRUZ, and YF-vax vaccines, respectively. ev locus-specific PCR testing of the vaccine-associated chicken substrate DNA was positive both for the nondefective ev-12 locus in two vaccines and for the defective ev-1 locus in all three vaccines. Both intact and ev-1 pol sequences were also identified in the particle-associated RNA. To investigate the risks of transmission, serum samples from 43 YF vaccine recipients were studied. None of the samples were seropositive by an ALV-E-based Western blot assay or had detectable EAV or ALV-E RNA sequences by RT-PCR. YF vaccines produced by the three manufacturers all have particles containing EAV genomes and various levels of defective or nondefective ALV-E sequences. The absence of evidence of infection with ALV-E or EAV in 43 YF vaccine recipients suggests low risks for transmission of these viruses, further supporting the safety of these vaccines.

Animals↗

Achieving national influenza vaccine targets--an investigation of the factors affecting influenza vaccine uptake in older people and people with diabetes.

A survey by postal questionnaire of a random sample of community residents with diabetes mellitus and those aged 75 years was undertaken in one Health Authority area to examine the factors associated with influenza vaccine uptake in these groups. The questionnaire sought: information on vaccine uptake and non-uptake over the previous three winter periods; patient attitudes to and knowledge about influenza and influenza vaccine; sources of patients' information; and patients' views on improving vaccine uptake. Self-reported vaccine uptake had increased in people with diabetes from 53.9% in 1997-98 to 67.6% in 1999-2000, and in people aged 75 years and over from 63.5% in 1997-98 to 70.2% in 1999-2000. Factors significantly associated with vaccine uptake in people with diabetes included a history of previous vaccination OR 40 (95% confidence interval 9,206), recommendation by a health professional OR 14 (2.9, 90) and belief that the vaccine protects against flu OR 5.6 (1.8, 18.9). Factors significantly associated with vaccine uptake in older people included the belief that the vaccine protects against flu OR 23 (8.4, 69.4), a history of previous vaccination OR 10 (3.9, 28.3) and not being concerned about side-effects OR 4 (2.1, 7.9). Information given by a health professional was the only source of information found to significantly influence vaccine uptake. Interventions suggested to increase uptake include provision of more information and better access to influenza vaccination. It is concluded that uptake rates for influenza vaccine have increased over the last three years to 67.4% in people with diabetes and 70.2% in people aged 75 and over. Professionals play a key role in influencing the decision to have influenza vaccine. Information about influenza and its vaccine needs to be combined with improvements in service provision if overall target uptake rates of 70% (65% in those aged 65 years and over) are to be achieved.

Aged↗

Gastrointestinal adverse reactions following anthrax vaccination: an analysis of the Vaccine Adverse Events Reporting System (VAERS) database.

BACKGROUND/AIMS: The Institute of Medicine (IOM) of the United States Academy of Sciences in 2000 encouraged the evaluation of active long-term monitoring studies of large populations to further evaluate the relative safety of anthrax vaccine. Anthrax is a deadly bacterial infectious disease that currently has been engineered as a biological warfare agent. The vaccine produced against anthrax is a cell-free crude culture of the various toxin components of the natural disease. The U.S. military current goal is to vaccinate its entire personnel by 2003. The purpose of this study was to evaluate anthrax vaccination and its association with arthritic, immunological and gastrointestinal adverse reactions based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database. METHODOLOGY: We analyzed the VAERS database from 15 December 1997 to 12 April 2000. We also compared the incidence of anthrax adverse reactions with the incidence of adverse reactions reported to VAERS after adult tetanus vaccination. RESULTS: Anthrax vaccine was one of the most reactogenic vaccines included in VAERS. The incidence of adverse reactions reported following anthrax vaccine was higher for every reaction analyzed in comparison to the adult vaccine control groups. CONCLUSIONS: The current anthrax vaccine may be acceptable in military populations in impending threat of anthrax exposure, the cost-benefits of vaccination in less high risk military populations may be more questionable. Civilian anthrax vaccination will require a less reactogenic vaccine. Civilian doctors should be aware of anthrax vaccine adverse reactions. Military and civilian doctors should also be diligent in their reporting to VAERS of cases of adverse reactions to anthrax vaccine.

Adult↗

[Local and systemic antibody response after vaccination with 3 different types of vaccines against influenza I. Hemagglutinationinhibiting antibodies (author's transl)].

A comparative study on the formation of hemagglutination inhibiting antibodies after vaccination with 3 different types of Influenza Vaccines (Whole virion, Splitvirion, and Subunit type) was performed in adults and children. The study populations were homogeneous as regards age and pre-immunization antibody profile. The following results were obtained: 1) Strain specific conversion rates for the A component (A/Victoria/3/75 H3N2) were 77% with the whole virion vaccine, 79% with the Splitvirion vaccine and 91% with the Subunit vaccine. The antibody conversion factors calculated on the basis of the geometric mean titers (GMT) were 5.0, 6,7 and 9.0 respectively. A fourfold increase in titers was observed in 68% of vaccinees with the whole virion vaccine, in 55% of vaccinees with the Splitvirion vaccine, and in 70% of vaccinees with the Subunit vaccine. 2) Local antibody formation on the basis of conversion rates yielded values of 18% (whole virion), 22% (Splitvirion), and 28% (Subunit vaccine). 3) Systemic antibody responses revealed predominantly strain and subtype specificity as opposed to local antibody formation which was also directed towards older sybtypes. This phenomenon was more pronounced in adults than in children. 4) A significant correlation was found between the local antibody production and the concentration of hemagglutination inhibiting serum antibodies as well as between the IgA concentration in nasal wash fluid and the percentage of individuals exhibiting local antibody formation in the upper respiratory tract system. 5) In children 6-14 years of age the antibody conversion rates were found to be 91-100% for the A component with the 3 vaccines under study. The GMT for the respective vaccines A, B and S ranged from 1:170 over 1:139 to 1:211. 6) With regard to the induction of hemagglutination inhibiting antibodies to the B component of the vaccine (B/Hongkong/8/73) either vaccine proved to be of insufficinet potency. Though conversion rates of 6/ to 77% (60-90% in children) were observed the GMT range was only 1:17 to 1:21 (1:21 to 1:35 in children). Only 29 to 35% of the adults and about one half of the children developed antibodies of greater than or equal to 1:40 after vaccination. With regard to this observation it has to be discussed whether one shouldn't consider monovalent A vaccines for future use in influenza vaccination campaigns.

Adolescent↗

Tuberculin sensitivity and skin lesions in children after vaccination with two batches of BCG vaccine.

BCG is one of the vaccines used, as control arm, in an ongoing large scale comparative leprosy vaccine trial in South India. The objective of the present study was to examine, in the local population, the sensitizing ability, as measured by skin test reactions to tuberculin, and reactogenecity, in terms of skin lesions at the site of vaccination, for the two batches of BCG vaccine used in the above trial. The study was undertaken in 816 tuberculin-negative, previously not vaccinated school children, aged five to 14 years. Each child received one of the two batches of BCG vaccine or normal saline (control), by random allocation. At 12 weeks from vaccination, character and size of local response, at the vaccination site, were recorded. At the same time, the children were retested with tuberculin and post-vaccination reactions to the test were measured after 72 hours. At three years after vaccination all available children were re-examined for the presence and size of BCG scar at the site of vaccination. It was found that healing of vaccination lesions was uneventful, with both batches of BCG. The mean size of the lesion was similar for the two batches, the overall mean being 6.3 mm. The mean size of post-vaccination tuberculin sensitivity increased with age, and it was 14.5 mm and 15.6 mm. The sensitizing effect attributable to the vaccine was 11 mm and 12 mm, for the two batches of BCG respectively. This study showed that the two batches of BCG, in a dose of 0.1 mg, used in the ongoing leprosy vaccine trial were acceptable in terms of vaccination lesion and were highly satisfactory in terms of development of hypersensitivity.

Adolescent↗

Vaccine safety versus vaccine efficacy in mass immunisation programmes.

In community-wide immunisation programmes against childhood infections there is a conflict between the interests of the individual (vaccine safety and efficacy) and the interests of the community (vaccine uptake and level of herd immunity). Studies suggesting that the complication rate is greater with the high efficacy Urabe Am 9 mumps vaccine than with the lower efficacy Jeryl Lynn vaccine, have led to concern about whether the higher efficacy mumps vaccine should be introduced or retained in nationwide mass immunisation programmes. We describe the use of a mathematical model to assess benefits and risks to both individual and community, and illustrate this method by reference to immunisation programmes based on these vaccines. On the basis of current epidemiological data on viral transmission and vaccine coverage in England and Wales, data on vaccine-associated and infection-associated complication rates, and vaccine efficacies estimated from clinical trials, our analyses suggest there is little to choose between the two vaccines, but that overall performance depends on the level of vaccine coverage in a defined population. In community-based programmes, the greater apparent safety of the Jeryl Lynn vaccine (fewer vaccine-induced complications) is offset by the greater apparent efficacy of the Urabe Am 9 vaccine (fewer complications due to natural infection). The findings suggest that it may not always be in the interests of the community to use the vaccine with the lowest complication rate.

Age Factors↗

Effect of vaccination route and composition of DNA vaccine on the induction of protective immunity against pseudorabies infection in pigs.

Vaccination with naked DNA may be an alternative to conventional vaccines because it combines the efficacy of attenuated vaccines with the biological safety of inactivated vaccines. We recently showed that the vaccination with naked DNA coding for the immunorelevant glycoprotein D (gD) of pseudorabies virus (PRV) induced both antibody and cell-mediated immunity in pigs and provided protection against challenge infection. To determine whether the efficacy of the naked DNA vaccination against PRV could be improved, we compared three sets of variables. First, the efficacy of the naked DNA vaccine coding only for the immunorelevant gD was compared with a cocktail vaccine containing additional plasmids coding for two other immunorelevant glycoproteins, gB and gC. Second, the intramuscular route of vaccination was compared with the intradermal route. Third, the commonly used needle method of inoculation was compared with the needleless Pigjet injector method. Five groups of five pigs were vaccinated three times at 4-weeks intervals and challenged with the virulent NIA-3 strain of PRV 6 weeks after the last vaccination. Results showed that although the cocktail vaccine induced stronger cell-mediated immune responses than the vaccine containing only gD plasmid, both vaccines protected pigs equally well against challenge infection. Intradermal inoculation with a needle induced significantly stronger antibody and cell-mediated immune responses and better protection against challenge infection than intramuscular inoculation. Our data show that the route of administering DNA vaccines in pigs is important for an optimal induction of protective immunity.

Animals↗

Impact of field vaccination with a Theileria annulata schizont cell culture vaccine on the epidemiology of tropical theileriosis.

Tropical theileriosis, caused by Theileria annulata, is an important tick-borne disease of cattle. A cell culture attenuated vaccine has been developed in our laboratory by long-term in vitro propagation of the schizont stage of the parasite. A longitudinal study was conducted at selected farms housing indigenous, cross-bred and exotic animals to investigate the effect of vaccination on the epidemiology of the disease. A total of 120 animals in 4 age groups were vaccinated with the vaccine before the onset of disease season. An equal number of age-matched animals were kept as controls at the same sites. Animals were monitored for 14 months at monthly intervals. The 97.5% vaccinated animals showed a rise in antibody titres 1 month post-vaccination, as determined by single dilution ELISA. The 78.3% of non-vaccinated animals became sero-positive over the period of observation. Mean antibody titres were significantly higher in vaccinated than non-vaccinated animals. Cross-bred animals showed higher antibody titres followed by exotic and indigenous animals in both the vaccinated and non-vaccinated groups. However, the antibody titres in animals of different ages were similar. The 36.7% vaccinated and 64.2% non-vaccinated animals became carriers (<0.5% piroplasms in erythrocytes) during the observation period. Clinical cases of theileriosis were recorded only in the non-vaccinated group suggesting that vaccinated animals were sufficiently immune to withstand field tick challenge for at least 14 months.

Animals↗

Prevention of transplacental transmission of moderate-virulent classical swine fever virus after single or double vaccination with an E2 subunit vaccine.

The use of a vaccine against classical swine fever virus (CSFV) during an outbreak of CSF should lead to a reduction in the horizontal or vertical transmission of CSFV. The reduction of vertical, i.e. transplacental, transmission of a moderate-virulent strain of CSFV from the sow to its offspring was studied in sows vaccinated once or twice with a CSFV E2 subunit vaccine. Two groups of nine sows were vaccinated with one PD95 dose of the E2 subunit vaccine, approximately four weeks before insemination. A third group of nine inseminated sows served as controls. One group of nine sows were vaccinated again at two weeks after insemination. At ten weeks after the primary vaccination, approximately six weeks after insemination, all 27 sows were challenged intranasally with 10(5) TCID50 of a moderate-virulent strain of CSFV, the Van Zoelen strain. The sows were euthanized at five weeks after challenge, and samples from the sows and fetuses were collected for detection of CSFV. All 27 sows were in gestation at the time of slaughter, CSFV was detected in the fetuses of all unvaccinated sows but it was not detected in any of the samples collected from fetuses of the double-vaccinated sows. Virus was however recovered from the fetuses of one out of nine sows vaccinated once. All the sows, except four double-vaccinated sows, developed CSFV Erns antibodies. Transplacental transmission of CSFV was reduced significantly (p <0.001) in all vaccinated sows. When the results from the experiment were extrapolated to a herd level, it could be concluded that, with 95% certainty, approximately 11% (single vaccination) or 0% (double vaccination), confidence intervals of 0.01-0.44 and 0.0-0.30 respectively, of the pregnant sows would still not be protected against vertical transmission of moderate-virulent CSFV. We conclude that vaccination with the CSFV E2 subunit vaccine can reduce the transmission of moderate-virulent strain of CSFV from the sow to its offspring significantly.

Animals↗

Acellular pertussis vaccine as a booster dose for seventeen- to nineteen-month-old children immunized with either whole cell or acellular pertussis vaccine at two, four and six months of age.

The safety and immunogenicity of two formulations of an acellular pertussis vaccine as a booster at 17 to 19 months of age were assessed in children immunized at 2, 4 and 6 months of age with acellular or whole cell pertussis vaccine. In Study I 86 children primed with a five-component acellular vaccine combined with diphtheria and tetanus toxoids or with a whole cell pertussis-diphtheria-tetanus vaccine were boosted with the same vaccine. Local reactions (64% vs. 93%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) and systemic reactions (68% vs. 97%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) were less common after the fourth dose of acellular vaccine than after the fourth dose of whole cell vaccine. In Study II 96 children primed with either an acellular or whole cell pertussis vaccine were boosted with an acellular vaccine. Local adverse reactions after booster immunization with acellular vaccine were more common in children primed with acellular vaccine than those primed with whole cell vaccine (68% vs. 33%; relative risk, 2.1; 95% confidence interval, 1.3 to 3.3). Antibody response to pertussis toxin, filamentous hemagglutinin and fimbriae were higher before and 1 month after the booster dose in children primed with the acellular vaccine. We conclude that the acellular pertussis vaccine is safe and immunogenic when used for the booster dose in children primed with either whole cell or acellular vaccine but is associated with local reactions.

Analysis of Variance↗

In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory.

In a double-blind, randomized trial, 102 healthy elderly subjects were inoculated with one of four preparations: (i) intranasal bivalent live attenuated influenza vaccine containing cold-adapted A/Kawasaki/86 (H1N1) and cold-adapted A/Bethesda/85 (H3N2) viruses; (ii) parenteral trivalent inactivated subvirion vaccine containing A/Taiwan/86 (H1N1), A/Leningrad/86 (H3N2), and B/Ann Arbor/86 antigens; (iii) both vaccines; or (iv) placebo. To determine whether local or systemic immunization augmented mucosal immunologic memory, all volunteers were challenged intranasally 12 weeks later with the inactivated virus vaccine. We used a hemagglutination inhibition assay to measure antibodies in sera and a kinetic enzyme-linked immunosorbent assay to measure immunoglobulin G (IgG) and IgA antibodies in sera and nasal washes, respectively. In comparison with the live virus vaccine, the inactivated virus vaccine elicited higher and more frequent rises of serum antibodies, while nasal wash antibody responses were similar. The vaccine combination induced serum and local antibodies slightly more often than the inactivated vaccine alone did. Coadministration of live influenza A virus vaccine did not alter the serum antibody response to the influenza B virus component of the inactivated vaccine. The anamnestic nasal antibody response elicited by intranasal inactivated virus challenge did not differ in the live, inactivated, or combined vaccine groups from that observed in the placebo group not previously immunized. These results suggest that in elderly persons cold-adapted influenza A virus vaccines offer little advantage over inactivated virus vaccines in terms of inducing serum or secretory antibody or local immunological memory. Studies are needed to determine whether both vaccines in combination are more efficacious than inactivated vaccine alone in people in this age group.

Administration, Intranasal↗

Vaccination with a Shigella DNA vaccine vector induces antigen-specific CD8(+) T cells and antiviral protective immunity.

A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env (vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8(+)-T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8(+) T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since the Shigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8(+) T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.

AIDS Vaccines↗

Use of long-term vaccination with a killed vaccine to prevent fecal shedding of Mycobacterium avium subsp paratuberculosis in dairy herds.

OBJECTIVES: To determine whether vaccination with a killed vaccine prevents fecal shedding of Mycobacterium avium subsp paratuberculosis, to compare effectiveness of a culture and cull program in vaccinated and nonvaccinated herds, and to compare paratuberculosis-related preventive management in vaccinated and nonvaccinated herds. SAMPLE POPULATION: 58 commercial Dutch dairy herds. DESIGN: Cross-sectional study (study A) in vaccinated (n = 25) and nonvaccinated (29) herds of dairy cows. Longitudinal study (study B) in vaccinated (n = 2) and nonvaccinated (2) herds of dairy cows. PROCEDURE: In study A, fecal samples were obtained from adult cows in herds with and without a history of vaccination with a killed vaccine. Management measures were evaluated. In study B, fecal samples were obtained 4 times at 6-month intervals from cows older than 6 months. Cows that had positive test results were removed from the herd directly after the outcome of the culture. RESULTS: In study A, differences were not detected among the 25 herds that were vaccinated; culture results were positive for M avium subsp paratuberculosis in 4.4% of herds. In 29 herds that had not been vaccinated, culture results were positive in 6.7%. In study B, the percentage of positive results on culture decreased from 10.9% and 5.7% to 3.5% and 0%, respectively in the 2 vaccinated herds. In the 2 nonvaccinated herds, percentages decreased from 6.1% and 16.5% to 0% and 2.3%, respectively. Management practices were different between herds that were vaccinated and herds that were not; owners of herds that were not vaccinated followed more preventive management procedures and practiced less feeding of raw milk to calves. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination of calves with a killed vaccine does not prevent transmission of M avium subsp paratuberculosis; therefore, hygienic practices remain essential in herd management.

Animal Husbandry↗

Evaluation of live attenuated varicella vaccine (Oka-RIT strain) and combined varicella and MMR vaccination in 13-17-month-old children.

The Oka-RIT strain of live attenuated varicella vaccine at dose levels 5300 PFU (high titre) and 2000 PFU (low titre) was tested in 13-17-month-old children; 50% of the children received the varicella vaccine alone, and the other 50% received it together with a measles-mumps-rubella (MMR) vaccine. The high titre and low titre varicella vaccines induced 96% and 92% seroconversion rates, respectively. Following combined vaccination with MMR, the corresponding seroconversion rates for varicella were significantly lower at 85% and 72% respectively. Seroconversion rates to measles, mumps and rubella were not affected by the combination of varicella vaccine plus MMR vaccination. Single varicella vaccine at both titre levels was found safe, although 10% of the children had minor skin reactions, possibly attributable to the vaccine. Reactions typically associated with MMR vaccination did not significantly increase after the combined varicella plus MMR vaccination. This study confirmed that the Oka-RIT strain varicella vaccine is safe and immunogenic in healthy young children, but failed to find a totally satisfactory combination for a varicella-MMR vaccine.

Antibodies, Viral↗

Japanese encephalitis vaccines: current vaccines and future prospects.

Vaccination against JE ideally should be practiced in all areas of Asia where the virus is responsible for human disease. The WHO has placed a high priority on the development of a new vaccine for prevention of JE. Some countries in Asia (Japan, South Korea, North Korea, Taiwan, Vietnam, Thailand, and the PRC) manufacture JE vaccines and practice childhood immunization, while other countries suffering endemic or epidemic disease (India, Nepal, Laos, Cambodia, Bangladesh, Myanmar, Malaysia, Indonesia and the Philippines) have no JE vaccine manufacturing or policy for use. With the exception of the PRC, all countries practicing JE vaccination use formalin inactivated mouse brain vaccines, which are relatively expensive and are associated with rare but clinically significant allergic and neurological adverse events. New inactivated JE vaccines manufactured in Vero cells are in advanced preclinical or early clinical development in Japan, South Korea, Taiwan, and the PRC. An empirically derived, live attenuated vaccine (SA14-14-2) is widely used in the PRC. Trials in the PRC have shown SA14-14-2 to be safe and effective when administered in a two-dose regimen, but regulatory concerns over manufacturing and control have restricted international distribution. The genetic basis of attenuation of SA14-14-2 has been partially defined. A new live attenuated vaccine (ChimeriVax-JE) that uses a reliable flavivirus vaccine--yellow fever 17D--as a live vector for the envelope genes of SA14-14-2 virus is in early clinical trials and appears to be well tolerated and immunogenic after a single dose. Vaccinia and avipox vectored vaccines have also been tested clinically, but are no longer being pursued due to restricted effectiveness mediated by anti-vector immunity. Other approaches to JE vaccines--including naked DNA, oral vaccination, and recombinant subunit vaccines--have been reviewed.

Animals↗

A fully liquid diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis--Haemophilus influenzae type b conjugate vaccine: immunogenicity and safety of primary vaccination in Taiwanese infants.

OBJECTIVE: To assess the immunogenicity of a fully liquid diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae type b (DTaP-IPV-Hib) conjugate vaccine compared to DTaP-IPV and lyophilized Hib conjugate vaccines given simultaneously at separate sites as a three-dose primary vaccination in Taiwanese infants. METHODS: Two hundred infants were randomized to receive either DTaP-IPV-Hib or DTaP-IPV plus Hib vaccine at 2, 4, and 6 months of age. Both combined vaccines contained the same five pertussis antigens: pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), fimbriae 2 and 3 (FIM 2&3). Antibody concentrations were measured before the first and after the third dose. Reactogenicity was evaluated from parental reports. All subjects received hepatitis B vaccine at 0, 1, and 6 months of age following the national vaccination schedule of Taiwan. RESULTS: The immunogenicity after the third dose was high for each vaccine antigen in both groups, and the vaccines had low reactogenicity. Statistical analysis showed no differences in the immune responses to the fully liquid DTaP-IPV-Hib vaccine compared with those to the DTaP-IPV plus Hib control vaccines, notably the anti-PRP (polyribose ribitol phosphate capsular polysaccharide) response, with 97-99% of infants having concentrations >or=1.0 microg/mL. Approximately 95% of all infants developed seroprotective levels of anti-hepatitis B surface antigen (HBs) antibodies (>or=10 mIU/mL). CONCLUSIONS: Both combination vaccines had similar high immunogenicity for each antigen, and both were well tolerated. Thus, inclusion of a Haemophilus influenzae type b conjugate vaccine in the combination did not result in clinically significant decrease in the PRP response or increase reactogenicity. The fully liquid pentavalent vaccine has the advantages of not requiring reconstitution and of administration as a single injection.

Diphtheria-Tetanus-acellular Pertussis Vaccines↗