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Pneumococcal vaccine for asthma.

BACKGROUND: Infection with Streptococcus pneumoniae is an important cause of pneumonia and other serious illnesses, particularly amongst those with certain high-risk medical conditions such as asthma. Although pneumococcal vaccine is routinely advocated for people with asthma, there is uncertainty about the evidence base that underpins this recommendation. OBJECTIVES: To determine the efficacy of pneumococcal vaccine in reducing mortality or morbidity from pneumococcal disease in asthmatics. SEARCH STRATEGY: Randomised controlled trials were identified using the Cochrane Airways Group's register derived from MEDLINE, EMBASE, and CINAHL electronic databases and hand searched respiratory journals and meeting abstracts. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, in which pneumococcal vaccine has been compared with placebo or no treatment in people with clinician diagnosed asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all abstracts and full papers of all articles of potential relevance were retrieved. Methodological quality was rated using the Cochrane approach and the Jadad rating scale. Data extraction was performed by one reviewer and checked independently by a second. We planned to perform quantitative analyses of outcomes on an intention-to-treat basis, where possible. MAIN RESULTS: Of the three papers retrieved, only one satisfied the inclusion criteria and the methodological quality of this study was low (unblinded and inadequate allocation concealment). None of the data could be aggregated in a meta-analysis. Comparisons in a sub-set of 30 asthmatic children prone to recurrent episodes of otitis media, showed that pneumococcal vaccination decreased the incidence of acute asthma exacerbations from 10 to 7 (per child per year). REVIEWER'S CONCLUSIONS: This review found very limited evidence to support the routine use of pneumococcal vaccine in people with asthma. A randomised trial of vaccine efficacy in children and adults with asthma is needed.

Asthma↗

Immunogenicity of 20 micrograms of recombinant DNA hepatitis B vaccine in healthy neonates: a comparison of three different vaccination schemes.

The immunogenicity of a full dose (20 micrograms) of recombinant DNA yeast-derived hepatitis B vaccine (Engerix-B) was assessed in healthy neonates in order to compare three candidate vaccination schemes. After randomization 162 newborns of hepatitis B surface antigen (HBsAg) negative mothers entered the study. Neonates received hepatitis B vaccine according to a four-dose vaccination scheme starting either at month 3 (scheme I: months 3, 4, 5, and 11) or at birth (scheme III: months 0, 1, 2, and 11). Another group of neonates received hepatitis B vaccine according to a three-dose scheme starting at birth (scheme II: months 0, 1, and 6). Serious adverse reactions were not observed; 2.5% of the vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of vaccination scheme; all infants developed anti-HBs levels > or = 10 IU/L, 97% > or = 100 IU/L. The immunogenicity of hepatitis B vaccine after primary and booster vaccinations, administered in the four-dose scheme started at birth, was significantly higher (P < 0.05) than in the three-dose scheme started at birth. Hepatitis B vaccination according to the four-dose scheme started at month 3 produced significantly higher (P < 0.05) antibody levels in comparison to the four-dose scheme started directly after birth. This study showed that a four-dose hepatitis B vaccination scheme starting at month 3 resulted in the highest antibody levels of the three schemes investigated and can be recommended for incorporation in the Expanded Programme on Immunization in The Netherlands.

Female↗

Comparative study on the immunogenicity between recombinant MS-Sj26GST vaccine and recombinant BCG-Sj26GST vaccine in Schistosoma japonicum.

The BALB/c mice were immunized with rMS-Sj26GST and rBCG-Sj26GST vaccine in Schistosoma japonicum by subcutaneous injection. After they were immunized for 8 weeks, the eyeballs were removed to get blood and macrophages of abdominal cavity and spleen cells were harvested. The lymphocytic stimulating index (SI) was used to measure the cellular proliferating ability and NO release was used to measure the phagocytic activity of the macrophages. By using ELISA kit, the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in serum and the splenic lymphocytic cultured supernatant were detected. The results showed that after the mice were immunized with 10(6) CFU of rMS-Sj26GST and rBCG-Sj26GST vaccine separately by subcutaneous injection, proliferating ability of splenic lymphocytes in the mice showed no difference (P > 0.05), but both were significantly increased as compared with that in the control group (P < 0.05); The contents of NO in the intraperitoneal macrophages of rMS-Sj26GST vaccine group were significantly lower than in the control group (P < 0.001) and rBCG-Sj26GST vaccine group (P < 0.01); The levels of serum IL-2 in the rMS-Sj26GST vaccine group were significantly increased as compared with that in the control group (P < 0.001), vector group (P < 0.01) and rBCG-Sj26GST vaccine group (P < 0.05); The contents of serum IFN-gamma in the rMS-Sj26GST vaccine group were significantly increased as compared with that in the control group (P < 0.01) and rBCG-Sj26GST vaccine group (P < 0.05), The contents of IFN-gamma in the cultured supernatant were significantly lower than those of rBCG-Sj26GST vaccine group (P < 0.001), but were significantly increased as compared with that in the control group (P < 0.01). It was indicated that both vaccines could enhance the immune response of the mice, but rMS-Sj26GST vaccine had stronger immunogenicity than rBCG-Sj26GST vaccine.

Animals↗

Enhanced immunogenicity to food-and-mouth disease virus in mice vaccination with alphaviral replicon-based DNA vaccine expressing the capsid precursor polypeptide (P1).

Recently, alphavirus replicon-based DNA vaccines, also known as suicidal DNA vaccines, have emerged as an important strategy to enhance the potency of DNA vaccines. In this study, two different types of DNA vaccines encoding the capsid precursor polypeptide (P1) of foot-and-mouth disease virus (FMDV) were constructed and the immunogenicity were investigated and compared in mouse model. The first DNA vaccine, pcDP1, is a conventional plasmid DNA vaccine in which P1 was driven directly by a cytomegalovirus promoter. The second DNA vaccine, pSCAP1, is a Semliki Forest virus (SFV) replicon-based DNA vaccine encoding the same antigen. In vitro expression and characterization indicated that two vaccine vectors could correctly produce the P1 antigen. However, pSCAP1 could induce obvious apoptosis of the transfected cells. After immunization in BALB/c mice, the P1-specific ELISA antibodies, neutralizing antibodies, as well as lymphocyte proliferative responses induced by pSCAP1 were significantly higher than those obtained in mice immunized with pcDP1. Notably, mice immunized with the pSCAP1 had the determined ability of clearing virus in their sera after FMDV challenge. These results indicate that the SFV replicon-based DNA vaccine pSCAP1 are more effective than conventional DNA vaccine and it can be considered a promising approach for the development of a safety and efficacious vaccine against FMDV.

Alphavirus↗

Antibody responses by cattle after vaccination with commercial viral vaccines containing bovine herpesvirus-1, bovine viral diarrhea virus, parainfluenza-3 virus, and bovine respiratory syncytial virus immunogens and subsequent revaccination at day 140.

Calves were vaccinated with four different commercial viral vaccines containing bovine herpesvirus-1 (BHV-1), bovine viral diarrhea (BVDV), parainfluenza-3 virus (PI-3V), and bovine respiratory syncytial virus (BRSV) immunogens. For the initial vaccination certain vaccines were given twice (days 0 and 28), whereas other vaccines were given on day 0. The calves received another injection on day 140 with the vaccine originally given on day 0. The sera were collected at days 0, 7, 14, 21, 28, 42, 56, 84, 112, 140, 154, 168, and 196 and assayed for viral neutralizing antibodies. The calves were seronegative to BHV-1, BVDV, and BRSV at the onset of the experiment; however, the calves were PI-3V antibody positive due to prior active infection. The commercial vaccines were: (I) inactivated; (II) modified live virus (MLV); (III) combination of chemically altered live virus, MLV, and inactivated virus; and (IV) combination of inactivated and MLV. Among the vaccine groups there were differences in onset and duration of antibodies as measured by geometric mean titers to each immunogen in postvaccination collection dates compared to day 0 titers; and likewise compared to day 140 titers after revaccination at day 140. There were also differences in antibody titers to the various viruses among the vaccine groups on specific collection dates. All four vaccines induced increased BHV-1 antibodies by day 14 after the initial injection. The antibody titers induced by MLV BHV-1 and the chemically altered BHV-1 vaccines had greater duration than those induced by the inactivated vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Safety of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussis-containing vaccine.

OBJECTIVE: The safety of a booster dose of a reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap) vaccine was evaluated in adolescents previously vaccinated with five doses of acellular pertussis-containing vaccine. STUDY DESIGN: Adolescents (n = 319) previously vaccinated with either 5 doses of diphtheria-tetanus-acellular pertussis (DTaP) (n = 193) or 4 doses of DTaP plus another acellular pertussis-containing vaccine received one dose each of Tdap and hepatitis A vaccine in a double-blinded, randomized, crossover trial. Rates of adverse events (AEs) after vaccination with Tdap versus hepatitis A and rates of local AEs among adolescents vaccinated with Tdap (sixth acellular pertussis-containing vaccine dose) versus rates in these same individuals after vaccination with their fifth DTaP dose were assessed. RESULTS: After Tdap, pain (63.6%), redness (51.7%), and swelling (41.4%) were the most frequently reported AEs. Large injection site swelling (swelling > 100 mm, arm circumference increase > 50 mm or diffuse swelling interfering with daily activities) occurred in three adolescents and resolved without sequelae. After the sixth dose of acellular pertussis-containing vaccine, adolescents reported more pain and less redness and swelling compared with incidences of these AEs reported when these same individuals received their fifth DTaP dose. CONCLUSIONS: These results suggest that Tdap is well tolerated as a sixth consecutive dose of acellular pertussis-containing vaccine.

Adolescent↗

Immunization of eyed channel catfish, Ictalurus punctatus, eggs with monovalent Flavobacterium columnare vaccine and bivalent F. columnare and Edwardsiella ictaluri vaccine.

The efficacy of a modified live monovalent Flavobacterium columnare vaccine and bivalent F. columnare and Edwardsiella ictaluri vaccines were evaluated following immersion vaccination of eyed channel catfish (Ictalurus punctatus) eggs. The modified live F. columnare vaccine was grown in modified Shieh broth and administered at 1.35 x 10(7) CFU/ml for 15 min exposure (1l water). Booster immunization was conducted at day 34 with 2.17 x 10(7) CFU/ml for 15 min. Bivalent vaccines consisted of a 1:1 ratio of the modified live F. columnare and AQUAVAC-ESC vaccine for the 15 min exposure (1l immersion bath). Non-vaccinated controls were held in 1l water without vaccine for 15 min. Fish were challenged with F. columnare (ALG-00-530) by immersion at days 109, 116, and 137 post-primary immunization or E. ictaluri (AL-93-75) by immersion at day 116 (bivalent vaccine group). Efficacy of monovalent modified live F. columnare vaccine administered singly or with a booster vaccination was shown to be protective with relative percent survival (RPS) values ranging from 50.0 to 76.8. Some variation was seen in RPS values following bivalent immunization, ranging from 33.0 to 59.7 in the fish challenged with F. columnare and 44.5 to 66.7 in fish challenged with E. ictaluri. However, the RPS values were not statistically different. The results suggest that administration of live bivalent vaccine at the eyed-egg stage is safe and elicits protection upon single pathogen challenge.

Animals↗

Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza.

BACKGROUND: In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat to human beings. A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines. METHODS: 32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 microg haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination. FINDINGS: The A/Duck/SIngapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 microgram doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 microg doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus. INTERPRETATION: Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 microg haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.

Adult↗

A multi-center controlled study of rapid hepatitis B vaccination using a novel triple antigen recombinant vaccine.

Hepatitis B vaccines have been available for 20 years, however, the disease still remains a global problem. Clearly, the protection of at-risk groups could be improved if a more potent vaccine with a shorter vaccination regimen were available. Hepacare is new recombinant vaccine, which contains three of the surface antigens of the HB virus and has higher immunogenicity than present single antigen (HBsAg only) vaccines. This study evaluates the potential for developing seroprotection rapidly and the viability of a 1 month/two dose regimen. A total of 400 adult subjects were vaccinated using either the present accelerated 2 month/three dose regimen of Engerix-B or a 1 month/two dose regimen of a novel triple antigen vaccine (Hepacare). Both vaccines were well tolerated. Four weeks after a single dose, the seroprotective rates for Engerix-B and the triple antigen vaccine were 5 and 17%, respectively. By month 2, 4 weeks after two doses of vaccine, it was 38 and 61%. Finally by month 3, 4 weeks after a third dose of Engerix-B or placebo, respectively, the seroprotection rates were 71 and 82%. The geometric mean titres (GMTs), of these responders was then 119 and 120 IU/l, respectively. Both vaccines were well tolerated. At all points up to and including 3 months after beginning vaccination, the novel 1 month/two dose regimen of Hepacare was significantly more effective in producing seroporotective titres than the 2 month/three dose regimen of Engerix-B (P = 0.001).

Adolescent↗

Kinetics of humoral immune response after rabies VR-G oral vaccination of captive fox cubs (Vulpes vulpes) with or without maternally derived antibodies against the vaccine.

In western Europe during the spring, the largest proportion of fox populations are cubs and the key to successful rabies oral vaccination campaigns is cub vaccination. In this paper we report on studies of the serology of 93 fox (Vulpes vulpes) cubs born to unvaccinated and orally vaccinated captive vixens, some of which were orally vaccinated at 30 or at 90 days of age with the vaccinia recombinant vaccine (VR-G) that expresses the rabies virus glycoprotein. The duration of cub passively acquired antibody, the development of immune responses to oral vaccination at either 30 or 90 days of age, possible interference between passive and active immunity to such vaccination and resistance to a potentially lethal rabies challenge dose when five months old were measured. The study showed that rabies neutralising antibody can be passed to their cubs by vixens orally vaccinated with VR-G during pregnancy. Maternally derived antibody titres in cubs declined with time and disappeared by 45-75 days after birth. Thirty days old cubs serologically responded to oral vaccination. No interference between antibody of maternal origin and active immunity conferred by VR-G oral vaccination or between antibody of maternal origin and protection was observed. Thus, very young cub immunisation against rabies with VR-G per os is possible whatever the immune status of their mothers. Provided a vaccine-bait suitable for such young cubs exists, oral vaccination at den entrances with VR-G is a feasibility.

Administration, Oral↗

Secondary measles vaccine failures identified by measurement of IgG avidity: high occurrence among teenagers vaccinated at a young age.

Failure to seroconvert (primary vaccine failure) is believed to be the principal reason (approx. > 95%) why some vaccinees remain susceptible to measles and is often attributed to the persistence of maternal antibodies in children vaccinated at a young age. Avidity testing is able to separate primary from secondary vaccine failures (waning and/or incomplete immunity), but has not been utilized in measles epidemiology. Low-avidity (LA) and high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years, range 2-22 years) from an outbreak in 1988-9 in Finland were tested for measles-virus IgG avidity using a protein denaturating EIA. Severity of measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2 years, range 2-22 years). The patients with HA antibodies (n = 28) tended to have clinically mild measles and rapid IgG response. Among failures vaccinated at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA antibodies, respectively. When a single measles, mumps and rubella (MMR) vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14) showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15 months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of HA responses compared to MMR recipients. Apart from one municipality, where even re-vaccinees had high risk of primary infection, 89% (CI 69 to approximately 100) of the infected re-vaccinees had an HA response. Secondary measles-vaccine failures are more common than was more previously thought, particularly among individuals vaccinated in early life, long ago, and among re-vaccinees. Waning immunity even among individuals vaccinated after 15 months of age, without the boosting effect of natural infections should be considered a relevant possibility in future planning of vaccination against measles.

Adolescent↗

Effect of vaccination in the field with the Theileria annulata (Hisar) cell culture vaccine on young calves born during the winter season.

The responses were monitored of young crossbred calves vaccinated against tropical theileriosis during the winter against a field tick challenge in the disease season. Thirty-eight calves below 2 months of age, born after the end of the disease season, were selected at an organized farm. Twenty-five animals were vaccinated with Theileria annulata (Hisar) cell culture vaccine (developed at CCS HAU Hisar laboratory) after the end of the disease season and 13 calves were kept as non-vaccinated controls. These calves were observed for their susceptibility to theileriosis in the new disease season. There was an increase in antibody titre in 18 of the 25 vaccinated animals one month after vaccination. The antibody titre then declined gradually, but remained higher than those of the non-vaccinated animals at month 0. No fever or other clinical signs of tropical theileriosis were observed in any of the vaccinated animals. Nine out of 25 (36%) vaccinated calves showed occasional piroplasms (<0.5%) in blood smears. All the vaccinated animals withstood the field tick challenge. On the other hand, 9 of the 13 (69%) unvaccinated calves exhibited occasional piroplasms, and included three clinical cases of tropical theileriosis. These observations suggest that young crossbred calves vaccinated with the T. annulata (Hisar) cell culture vaccine at the end of the disease season were relatively resistant during the next disease season.

Animals↗

Compliance with hepatitis B vaccination in 1175 heroin users and risk factors associated with lack of vaccine response.

AIMS: To investigate the feasibility of hepatitis B vaccination among heroin users, assessing adherence to the vaccination schedules and identifying factors associated with antibody response. DESIGN AND PARTICIPANTS: A large cohort study in nine public centres for drug users (PCDUs) in north-eastern Italy, with data collected between January 1989 and December 1998. A total of 1175 heroin users were selected and vaccinated with a recombinant vaccine using two schedules (0-1-6 months and 0-1-2 months). FINDINGS: Eighty-eight per cent of patients completed the vaccination series and a protective antibody response occurred in 77% of subjects. Completion of the vaccination series was not related to the length of the vaccination schedule or whether the patient was still in drug abuse treatment at the end of the series, but was related strongly to the number of patients enrolled at each PCDU (Spearman correlation = - 0.93, P < 0.001). Four variables were significantly associated with lack of seroconversion in response to vaccination: older age (AOR = 0.91 per year, 95% CI 0.88-0.94, P < 0.001), 2-month vaccination schedule (AOR = 3.10, 95% CI 2.06-4.68, P < 0.001), HCV seropositivity (AOR = 0.69, 95% CI 0.47-0.99, P = 0.04), HIV seropositivity (AOR = 0.27, 95% CI 0.10-0.77, P = 0.01). CONCLUSIONS: A large-scale, multi-site hepatitis B vaccination programme for heroin users proved feasible and effective. The factors associated with a lack of antibody response may be useful in identifying patients who would benefit most from routine post-vaccination testing, with booster doses for non-responders. These results suggest that hepatitis B vaccination for drug users should become a routine public health practice.

Adult↗

Whole virus influenza vaccine activates dendritic cells (DC) and stimulates cytokine production by peripheral blood mononuclear cells (PBMC) while subunit vaccines support T cell proliferation.

Three types of trivalent influenza vaccines were analysed for their in vitro stimulatory properties on immune cells from young healthy volunteers. A whole inactivated virus (WV) vaccine, a conventional subunit (c-SU) preparation and a new virosomal subunit (v-SU) vaccine were used. Blood-derived DC up-regulated MHC class II, CD54, CD80 and CD86 after exposure to WV vaccine, indicating their functional maturation, but were only moderately affected by subunit (SU) vaccines. In addition, IL-12 and tumour necrosis factor-alpha (TNF-alpha) secretion by DC were markedly enhanced by WV, but not by SU vaccines. The production of IL-2 and interferon-gamma (IFN-gamma) by PBMC was also strongly stimulated by WV, but much less by SU vaccines, among which the v-SU vaccine was a better stimulator of IL-2 secretion. In contrast to WV vaccine both SU vaccines were powerful stimulators of PBMC proliferation. Our results suggest that the presence of influenza core components leads to the activation of DC and triggers the production of cytokines by PBMC. SU vaccines are in contrast excellent stimulators of T cell growth. A combination of WV and SU vaccines in immunization regimes might allow optimal T cell priming as well as the efficient generation and maintenance of memory cells.

Cell Division↗

Impact of the bloodborne pathogens standard on vaccination of healthcare workers with hepatitis B vaccine.

OBJECTIVES: To evaluate the impact of Occupational Safety and Health Administration (OSHA) regulations on the vaccination of healthcare workers (HCWs), to assess interpretation of these regulations, and to evaluate changes in hospital vaccination policies. DESIGN: Between June 1, 1992, and August 15, 1992, a telephone survey was conducted among 150 hospitals selected randomly from participants in the American Hospital Association 1991 annual survey. RESULTS: Of the 150 hospitals, 96 (64%) provided information on hepatitis B vaccination coverage of their employees. Of the 103,419 employees in these hospitals, 77,302 (75%) were eligible to receive the hepatitis B vaccine, and 38,850 (51%) of these were vaccinated completely (had received 3 doses of vaccine). Following issuance of the final regulations, 73% of hospitals reported greater employee acceptance of hepatitis B vaccine, and hospitals were more likely to offer hepatitis B vaccine to maintenance workers, security personnel, dietary staff, and clerical personnel. Seventy-five hospitals (50%) reported conducting postvaccination serologic testing on all hospital employees, 12 (8%) as a result of OSHA regulations. Twenty-three hospitals (16%) reported administering routine booster doses of hepatitis B vaccine at 3, 5, or 7 years. CONCLUSIONS: The new OSHA standard resulted in a greater awareness of risk for HBV infection among HCWs and an increase in the number of HCWs receiving hepatitis B vaccine; however, vaccination coverage remained suboptimal. Postvaccination serologic testing of employees with negligible risk and the routine administration of vaccine booster doses may be diverting resources and preventing comprehensive coverage of high-risk employees.

Blood-Borne Pathogens↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination.

A standard challenge with percutaneous smallpox vaccine was administered to 629 children six to 12 months after percutaneous primary inoculation with one of four vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membranes, the Lister vaccine, or the CV-1 strain). Of those who had had major reactions on primary vaccination, 8%-21% responded to revasccination with a typical primary-type skin response. In contrast, such a primary-type response occurred in 50% of those who on primary vaccination had developed serum antibody in the absence of major reactions and in 83% of those who had had no serologic or clinical evidence of primary "take." Skin lesions on revaccination tended to be largest in thosewhose primary vaccination was with CV-1, although fever and minor complications were not more frequent. Moreover, even in children who had received CV-1 vaccine, skin responses to challenge vaccine were clearly attenuated when compared with responses of children who had not had takes on primary vaccination. Sizes of lesions and acceleration of skin erytherma after challenge were related in most children to titers of both hemagglutination-inhibiting and neutralizing antibody at the time of revaccination. One month after revaccination, neutralizing antibody was present in 93%-96% of those with takes onprimary vaccination with New York City or Lister vaccines, but only 75% of CV-1 vaccines.

Antibody Formation↗

Neuraminidase content of influenza vaccines and neuraminidase antibody responses after vaccination of immunologically primed and unprimed populations.

Vaccines prepared with influenza A/swine/1976/37-like virus contained neuraminidase activity comparable to that of H3N2 vaccines, whereas little neuraminidase activity could be detected in influenza A/New Jersey/76 vaccines. In single-dose vaccine studies, A/swine/1976/37-like split-virus vaccine induced antibody to neuraminidase (NAAb) in about 20% of children younger than 18 years and this NAAb response was better than or equal to the antibody response to the vaccine's hemagglutinin (HAAb). In immunologically primed adults, the NAAb response to a single dose of Hsw1N1 or H3N2 vaccine was 38%-54%, but this value was about 1.7-fold lower than that for HAAb response. Children six to 17 years old given two doses of A/swine/1976/37-like vaccine had an overall 70% NAAb response, whereas children of similar age had an overall 30%-48% NAAb response to two doses of A/Victoria/3/75 (H3N2) virus. The findings support a hypothesis that the NAAb response to influenza vaccines can be suppressed if subjects receiving the vaccine are immunologically primed to its hemagglutinin component. NAAb responses in the absence of HAAb responses occur in only about 5% of vaccinated persons who are immunologically primed to both the hemagllutinin and neuraminidase of the vaccine.

Adolescent↗

Safety and immunogenicity of a combination diphtheria-tetanus toxoids-acellular pertussis-hepatitis B vaccine administered at two, four and six months of age compared with monovalent hepatitis B vaccine administered at birth, one month and six months of age.

OBJECTIVE: To evaluate the safety and immunogenicity of diphtheria-tetanus toxoids-acellular pertussis (DTPa)-hepatitis B (HepB) combination vaccine given at 2, 4 and 6 months of age compared with monovalent HepB vaccine given at birth, 1 month and 6 months of age and DTPa vaccine given at 2, 4 and 6 months of age. METHODS: Healthy infants were randomized to receive a combination DTPa-HepB vaccine (diphtheria and tetanus toxoids, acellular pertussis antigens and hepatitis B surface antigen), concomitantly with type b and oral poliovirus vaccines at 2, 4 and 6 months of age (Group 1) or HepB vaccine given at birth, 1 month and 6 months of age and DTPa, type b and oral poliovirus vaccines given at 2, 4 and 6 months of age (Group 2). Antibody responses were evaluated at birth, 2 months and 7 months of age. Safety was evaluated after each immunization using diary cards and parental interviews. RESULTS: One month after the third dose (7 months of age), the geometric mean concentration of antibody to hepatitis B surface antigen was approximately 3.5-fold higher in Group 2 than in Group 1 infants (3643 and 1052 mIU/ml, respectively; < 0.001). Nevertheless the rates of seroprotection to HepB (antibody to hepatitis B surface antigen > or =10 mIU/ml) in Groups 1 and 2 were similar, 99 and 100%, respectively. Also the postvaccination geometric mean concentrations and rates of seroprotection or vaccine response to all of the other vaccine antigens evaluated were similar or greater in Group 1 than in Group 2. The rates of adverse events were similar between the two groups, with fussiness and soreness at any injection site reported most frequently. CONCLUSIONS: The DTPa-HepB combination vaccine was safe and immunogenic when given to infants at 2, 4 and 6 months of age. Equivalent rates of seroprotection to hepatitis B were achieved despite a reduction of the interval between the second and third doses from 5 months in Group 2 to 2 months in Group 1. Hepatitis B-containing combination vaccines should reduce the number of vaccine injections required in childhood and maintain excellent seroprotection against multiple pathogens.

Age Factors↗