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Pneumococcal vaccine and HIV infection: report of a vaccine failure and reappraisal of its value in clinical practice.

A clinical failure of pneumococcal vaccine is reported. A 22 year old African woman was given 23-valent pneumococcal vaccine at her initial presentation with HIV infection. She was asymptomatic and had a CD4+ lymphocyte count above 500 cells/mm3. Eighteen months later she died of meningitis and septicaemia due to Streptococcus pneumoniae type 9 (an antigen included in the 23-valent vaccine). Pneumococcal antibody levels performed on stored blood demonstrated no serological response to the vaccine. This is the first reported case of clinical failure of pneumococcal vaccine in an HIV infected patient who received vaccine whilst at the asymptomatic stage of HIV infection and with relatively intact immune function. The literature pertaining to pneumococcal vaccination in the context of HIV infection was reviewed. Pneumococcal vaccination is recommended for HIV positive patients in the UK by the Departments of Health. It is likely that many physicians are not aware of these recommendations or are concerned about the poor efficacy of the vaccine, and it may consequently be underused in clinical practice. But the potential gain to the HIV positive patient is such that the vaccine should be offered to all HIV positive patients as soon as they present for medical care, irrespective of the stage of HIV disease. Physicians and patients should be aware that the vaccine is not fully protective and that episodes of sepsis, pneumonia and meningitis could still be pneumococcal in origin and should be treated appropriately. Awareness of the substantial risks of pneumococcal disease in HIV infected patients with prompt diagnosis and effective treatment is the most important strategy to decrease morbidity and mortality.

Adult↗

International meeting on cancer vaccines: how can we enhance efficacy of therapeutic vaccines?

The major aims of the International Meeting on Cancer Vaccines were to review the state-of-the-art research on cancer vaccines, to compare different experimental approaches of therapeutic vaccination and to discuss critical issues and perspectives. The results from recent clinical trials in patients treated with different types of cancer vaccines were presented. Reasons for the limited response and possible modalities for enhancing efficacy of therapeutic vaccines were subjects of major discussion. A consensus was achieved on the need of combining cancer vaccines with other anticancer treatments. Of note, evidence stemming from studies in animal models pointed out new rationales for a selective combination of cancer vaccines with chemotherapy. In addition, some main presentations focused on new adjuvants (CpG oligonucleotides) and on the role of cytokines (i.e., type I IFN, interleukin 12, and interleukin 15) in promoting an antitumor immune response to vaccines. A considerable attention was given to regulatory T cells and to strategies for suppressing their function, thus enhancing vaccine efficacy. An entire session was devoted to the use of dendritic cells for the development of cancer vaccines. The results of clinical studies and the advantages of using new modalities for preparing dendritic cell-based vaccines were discussed.

Cancer Vaccines↗

Rates of influenza vaccination in older adults and factors associated with vaccine use: a secondary analysis of the Canadian Study of Health and Aging.

BACKGROUND: Influenza vaccination has been shown to reduce morbidity and mortality in the older adult population. In Canada, vaccination rates remain suboptimal. We identified factors predictive of influenza vaccination, in order to determine which segments of the older adult population might be targeted to increase coverage in influenza vaccination programs. METHODS: The Canadian Study of Health and Aging (CSHA) is a population-based national cohort study of 10263 older adults (>/= 65) conducted in 1991. We used data from the 5007 community-dwelling participants in the CSHA without dementia for whom self-reported influenza vaccination status is known. RESULTS: Of 5007 respondents, 2763 (55.2%) reported having received an influenza vaccination within the previous 2 years. The largest predictive factors for flu vaccination included: being married (57.4 vs. 52.6%, p = 0.0007), having attained a higher education (11.0 vs. 10.3 years, p < 0.0001), smoking (57.1% vs. 52.9%, p = 0.0032), more alcohol use (57.9% of those who drank more vs. 53.2% of those who drank less, p = 0.001), poorer self-rated health (54.1% of those with good self-rated health vs. 60.6% of those with poor self-rated health, p = 0.0006), regular exercise (56.8% vs. 52.0%, p = 0.001), and urban living (55.8% vs. 51.0%, p = 0.03). While many other differences were statistically significant, most were small (e.g. mean age 75.1 vs. 74.6 years for immunized vs. unimmunized older adults, p = 0.006, higher Modified Mini Mental Status Examination score (89.9 vs. 89.1, p < 0.0001), higher comorbidity (2.7 vs. 2.3 comorbidities, p < 0.0001). Residents of Ontario were more likely (64.6%) to report vaccination (p < 0.0001), while those living in Quebec were less likely to do so (48.2%, p < 0.0001). Factors retaining significance in a multivariate analysis included older age, higher education, married status, drinking alcohol, smoking, engaging in regular exercise, and having higher comorbidity. CONCLUSIONS: The vaccination rate in this sample, in whom influenza vaccination is indicated, was low (55.2%). Even in a publicly administered health care setting, influenza vaccination did not reach an important proportion of the elderly population. Whether these differences reflect patient preference or access remains to be determined.

Aged↗

Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein--based vaccine.

PURPOSE: To evaluate the safety of an HER-2/neu intracellular domain (ICD) protein vaccine and to estimate whether vaccine dose impacts immunogenicity. PATIENTS AND METHODS: Twenty-nine patients with HER-2/neu-overexpressing breast or ovarian cancer and with no evidence of disease after standard therapy received a low- (25 microg), intermediate- (150 microg), or high-dose (900 microg) HER-2/neu ICD protein vaccine. The vaccine was administered intradermally, monthly for 6 months, with granulocyte-macrophage colony-stimulating factor as an adjuvant. Toxicity and both cellular and humoral HER-2/neu-specific immunity was evaluated. RESULTS: The vaccine was well tolerated. The majority of patients (89%) developed HER-2/neu ICD-specific T-cell immunity. The dose of vaccine did not predict the magnitude of the T-cell response. The majority of patients (82%) also developed HER-2/neu-specific immunoglobulin G antibody immunity. Vaccine dose did not predict magnitude or avidity of the HER-2/neu-specific humoral immune response. Time to development of detectable HER-2/neu-specific immunity, however, was significantly earlier for the high- versus low-dose vaccine group (P =.003). Over half the patients retained HER-2/neu-specific T-cell immunity 9 to 12 months after immunizations had ended. CONCLUSION: The HER-2/neu ICD protein vaccine was well tolerated and effective in eliciting HER-2/neu-specific T-cell and antibody immunity in the majority of breast and ovarian cancer patients who completed the vaccine regimen. Although the dose of vaccine did not impact the magnitude of T-cell or antibody immunity elicited, patients receiving the highest dose developed HER-2/neu-specific immunity more rapidly than those who received the lowest dose.

Adult↗

[Impact of systematic vaccination with the antimeningococcal C conjugated vaccine in a health area in Andalusia].

BACKGROUND: A retrospective longitudinal study of population incidence was made to assess the effectiveness of meningococcal serogroup C conjugate vaccine, after its mass introduction in children in the geographic area of a health district, measuring its population impact, and we have studied the state of the meningococcal disease. METHODS: Vaccine coverage in children born between 1991 and 2001, and rates of incidence in declared cases of meningococcal disease in seven epidemiological seasons (1997/98 to 2003/04) were calculated. The impact of vaccination against serogroup C meningitis was assessed comparing the average annual rates of previous and later seasons to the vaccination campaigns in population younger and older than 10, using the Fisher exact test. RESULTS: In all the study period, 109 cases of meningococcal disease were declared, of which 50 were of serogroup C meningococcal disease. Starting from 2000/2001 season the incidence of serogroup C disease decreased in the population below 10. In this age group, the annual average rate of post-vaccine seasons decreases in respect to pre-vaccine (from 8.2 to 2.0 per 100,000 inhabitants) showing a statistically significant difference. In the population above 10 years, this incidence reduction was not observed. In the study period, no case of vaccine failure was declared. CONCLUSIONS: The absence of vaccine failure and the impact observed on the incidence of serogroup C meningococcal disease in children under 10 suggests the effectiveness of this new conjugate vaccine, together with suitable vaccination conditions (vaccination schedule, high catch-up, etc.) which are developing in our health district.

Age Factors↗

Evaluation of shedding of bovine herpesvirus 1, bovine viral diarrhea virus 1, and bovine viral diarrhea virus 2 after vaccination of calves with a multivalent modified-live virus vaccine.

OBJECTIVE: To determine whether bovine herpesvirus 1 (BHV1), bovine viral diarrhea (BVDV) virus 1 (BVDV1), or BVDV 2 (BVDV2) were shed after parenteral administration of a multivalent modified-live virus vaccine. DESIGN: Prospective study. ANIMALS: 28 healthy beef calves and 4 healthy pregnant beef cows. PROCEDURE: A commercially available modified-live virus multivalent vaccine was administered to steers and heifers (n = 18) that were seronegative to BHV1, BVDV1, and BVDV2. Four seronegative pregnant control cows were held in contact with the vaccinated calves for 103 days. Unvaccinated calves (n = 10) were held as controls in a separate double-fenced pen. Seroconversion was monitored by determining serum neutralization titers after vaccination. Viral shedding and viremia were assessed via analysis of nasal swab specimens and blood by use of polymerase chain reaction (PCR) and reverse transcriptase-PCR assays and virus isolation. RESULTS: A transient BVDV1 viremia was detected in most vaccinated calves 3 to 10 days after vaccination. All vaccinated calves seroconverted to BVDV1 and BVDV2. Seventeen of 18 vaccinated calves seroconverted to BHV1. Viral shedding was not detected in the vaccinated calves. All control cattle remained seronegative to BHV1, BVDV1, and BVDV2 throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE: Shedding of BHV1, BVDV1, and BVDV2 after vaccination was either nonexistent or undetected and did not result in transmission of BHV1, BVDV1, or BVDV2 vaccine viruses to pregnant contact control cows.

Animals↗

[Immune response of suckling mouse brain (CRL) rabies vaccine and tissue culture rabies vaccine (Verorab) in pre-exposure prophylaxis in humans].

BACKGROUND: A WHO experts committee recommended the substitution of antirabic vaccines produced in nervous tissue, by vaccines produced in tissue cultures. AIM: To compare the immunogenic capacity of antirabic vaccines CRL (produced in nervous tissue) and Verorab (produced in tissue culture), used for pre-exposure prophylaxis in humans. PATIENTS AND METHODS: Fifty four volunteers were immunized for this study. The first group, vaccinated with CLR was treated with a scheme of 4 subcutaneous peri umbilical doses in days 0, 3, 7 and 28. The second group, vaccinated with Verorab vaccine was treated with a scheme of 3 intramuscular doses in deltoid zone at days 0, 7 and 28. Blood samples were obtained at days 0, 7, 42 and 365 to measure neutralizing antibodies using the Inhibition of Fluorescent Focus Technique (RFFIT). RESULTS: At day seven, a primary non protective immunologic response was observed in both groups, with titers significantly higher in the group vaccinated with Verorab. At day 42, no differences were observed. At day 365, all subjects vaccinated with Verorab and 50% of individuals vaccinated with CRL had protective antibody titers (p <0.05). CONCLUSIONS: The vaccine produced in cell breeds (Verorab) produces a better an faster immunologic response compared to the CRL vaccine.

Adult↗

Juvenile offenders and hepatitis B: risk, vaccine uptake and vaccination status.

OBJECTIVE: To determine the hepatitis B vaccination status of juvenile offenders in a custodial setting, their perceived risk of hepatitis B infection, and factors influencing vaccine uptake. DESIGN: 130 males aged 14-17 years resident at the Melbourne Juvenile Justice Centre for at least one week between mid-January and mid-December 1996 were invited to participate; 90 (69%) completed a doctor-administered questionnaire, and blood for serological testing was obtained from 83 of these participants. MAIN OUTCOME MEASURES: Whether hepatitis B vaccine had been offered; whether hepatitis B vaccine had been given; the presence of antibodies to hepatitis B and C; risk factors and self-perceived risk of hepatitis B. RESULTS: About a quarter of participants (22/83) had protective levels of antibody to hepatitis B surface antigen (anti-HBs). Forty (44%) participants reported having been offered hepatitis B vaccine; they were more likely to be vaccinated and have protective levels of anti-HBs. Perceived risk for bloodborne virus infection was low, although two-thirds of participants were at high risk of hepatitis B infection. On serological testing, 6.4% (5/78) were positive for antibody to hepatitis B core antigen (anti-HBc), and a further 2.6% (2) had equivocal antibody levels. Of the 71 who were negative for anti-HBc, 51 (71.8%) were negative for anti-HBs. CONCLUSIONS: The targeted hepatitis B vaccination program has not adequately protected this group at high lifetime risk of hepatitis B. Failure to deliver vaccine may reflect lack of contact with healthcare services, oversight in offering vaccine and reluctance of youth to participate in preventive healthcare measures, often through not seeing themselves to be at risk. Universal approaches to vaccination may be more successful in vaccinating this group.

Adolescent↗

Safety and immunogenicity of a candidate HIV-1 vaccine in healthy adults: recombinant glycoprotein (rgp) 120. A randomized, double-blind trial. NIAID AIDS Vaccine Evaluation Group.

OBJECTIVE: To evaluate the safety and immunogenicity of recombinant glycoprotein (rgp) 120, a candidate vaccine for the human immunodeficiency virus (HIV), formulated with a novel adjuvant, MF59, with or without a biological response modifier, MTP-PE. DESIGN: Multicenter, double-blind, randomized trial. SETTING: University medical centers. PARTICIPANTS: 49 healthy, HIV-seronegative volunteers 18 to 60 years of age who were at low risk for HIV type 1 (HIV-1) infection. INTERVENTIONS: In part A of the study, 32 participants were randomly assigned to receive either 15 micrograms of rgp 120 in MF59, 15 micrograms of rgp 120 in MF59 plus 50 micrograms of MTP-PE, 50 micrograms of rgp 120 in MF59, or 50 micrograms of rgp 120 in MF59 plus 50 micrograms of MTP-PE. Participants were vaccinated at 0, 1, 6, and 12 to 18 months. In part B, 17 participants were randomly assigned to receive five monthly injections of either 50 micrograms of rgp 120 in MF59 or MF59 alone followed by a booster injection at 12 to 18 months. MAIN OUTCOME MEASURES: Local and systemic reactions; laboratory measures of hepatic, renal, immunologic, and bone marrow toxicity; and HIV-specific serologic and cell-mediated immune responses. RESULTS: 13 patients in part A received 50-micrograms doses of rgp 120; type-specific neutralizing antibody responses against the SF-2 strain of HIV-1 (HIV-1/SF-2) were induced in all 13. Nine of the 13 had crossreactive neutralizing activity against the MN strain of HIV-1 (HIV-1/MN), and 2 had crossreactive neutralizing activity against the IIIB strain of HIV-1 (HIV-1/IIIB). Twelve patients had typespecific fusion inhibition activity; only 1 had crossreactive fusion inhibition activity against HIV-1/MN. The monthly vaccination schedule used in part B resulted in decreased antibody titers, indicating that a rest period in the schedule is necessary for maximal immunogenicity. Lymphoproliferative responses against gp120 were induced in all vaccine recipients. The stimulation index to gp120 was persistently greater than 15 for 6 months after the last booster vaccination was given. CD8+ cytotoxic T-lymphocyte activity was detected in 1 of the 11 participants tested. Vaccine that contained MTP-PE caused a greater number of moderate or severe local and systemic reactions (of 16 participants, 4 had local reactions and 13 had systemic reactions) than did vaccine formulated with MF59 alone (of 16 participants, 7 had local reactions [P < 0.01] and 0 had systemic reactions [P < 0.001]). CONCLUSIONS: The SF-2 rgp120 vaccine is safe and immunogenic. Three vaccinations with rgp120 in MF59 can induce type-specific and crossreactive neutralizing antibody against B-subtype laboratory strains of HIV-1. Human immunodeficiency virus-specific lymphoproliferative responses were induced in all vaccinated participants, and CD8+ cytotoxic T-lymphocyte activity was shown in one participant. A trend toward the augmentation of lymphoproliferative and humoral responses by MTP-PE was seen in the participants receiving 15 micrograms of rgp120. However, MTP-PE caused a statistically significant increase in the incidence of local and systemic side effects, which was felt to outweigh the small increase in immunogenicity provided by this biological response modifier in an otherwise well-tolerated vaccine.

AIDS Vaccines↗

Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine with a whole-cell killed vaccine in Malaysian Air Force recruits.

OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions.

Adolescent↗

[Persistence of serologic and allergic reactions in ewes after vaccination with the H.38 or Rev.1 vaccines in a brucellosis (Brucella melitensis) enzootic area].

In a flock of 2,000 ewes located in an endemic area of Brucella melitensis infection, subjected to systematic vaccination of lambs either with killed and adjuvanted B. melitensis H.38 vaccine from 1973 to 1978, or with living B. melitensis Rev.1 vaccine since 1979, reactions to allergic intrapalpebral test, complement fixation test and Rose Bengal plate test were recorded in small groups of animals vaccinated four, three, two or one years ago. Four years after H.38 vaccination, 39 ewes out of 40 (97%) remained positive at least to one of the three tests. After vaccination with strain Rev.1, 16% out of 153 ewes vaccinated one to four years before were positive. These results were discussed according to two aspects: 1) infectious or vaccinal origins of these positive reactions; 2) consequences on implement of test and slaughter procedures in a vaccinated flock: allergic or complement fixation tests would have led to eliminate 9% out of ewes vaccinated with the Rev.1 vaccine, but only 1% with the Rose Bengal plate test.

Animals↗

Immunity to Escherichia coli in pigs: antibody secretion by the mammary gland after intramammary or intramuscular vaccination with an E. coli vaccine.

Indirect hemagglutinating antibody titres in individual gland samples of colostrum and milk from 13 sows were measured. Five of the sows were vaccinated via a mammary gland and five by the intramuscular route with a live formalinised Escherichia coli vaccine and three remained as non-vaccinated controls. Antibody titres were higher in colostral and milk whey from the vaccinated sows than from non-vaccinated groups. The inoculated gland in the group of sows given vaccine by the intramammary route secreted milk containing markedly more antibodies to the vaccine E. coli strain than did the non-vaccinated glands. Milk from the vaccinated gland did not contain higher titres to heterologous E. coli O antigens than milk from non-vaccinated glands. Serum titres were the same or higher than the titres in colostrum from non-vaccinated glands.

Animals↗

Embryo vaccination of chickens with infectious bronchitis virus: histologic and ultrastructural lesion response and immunologic response to vaccination.

Chicken embryos 18 days of age and newly hatched chicks were vaccinated with an infectious bronchitis virus (IBV) vaccine (V-IBV) or with an IBV vaccine that had been serially passaged 40 times in chick kidney tissue culture (P-IBV). Immunologic and pathologic changes in the chicks were compared at selected intervals until the 35th day. Pathologic changes were evaluated by light, transmission, and scanning electron microscopy. Immunologic changes were assayed by a constant virus-diluting serum plaque-reduction test in chicken cell cultures, by 51Cr-release cytotoxicity assays, and by phytohemagglutination (PHA) responses. Embryos vaccinated with P-IBV and 1-day-old chicks vaccinated with V-IBV had similar transient lesions that were confined primarily to the trachea. Embryo vaccination and posthatch vaccination induced similar primary and secondary antibody responses in chicks. It was concluded that neither vaccination technique consistently influenced PHA response of whole blood cells or natural killer cell reactivity of spleen effector cells. Additionally, effector cells cytotoxic to IBV-infected target cells were not detected in chicks vaccinated as embryos or at hatch. The pathologic and immunologic effects of vaccination with P-IBV were comparable to those induced by conventional vaccination of chicks.

Animals↗

Measles/mumps/rubella vaccine (MMR): an audit of Leeds health professionals' knowledge of contraindications and intention to vaccinate assessed by postal questionnaire.

An audit of Leeds health professionals' knowledge of valid contraindications to measles/mumps/rubella (MMR) vaccine was undertaken by postal questionnaire, three months after its introduction. The health professional groups were health visitors, clinical medical officers, general practice trainers and general practice vocational trainees. The results indicate that some health professionals would give MMR vaccine to children when it was contraindicated (e.g. to a child receiving chemotherapy or radiotherapy). However, a much greater problem was the number of health professionals stating that they would not vaccinate children with MMR vaccine in clinical situations where there were no valid contraindications to its use. Some health professionals were also applying contraindications to the use of pertussis vaccine to the use of MMR vaccine. The information contained in the Joint Committee on Vaccination and Immunisation handbook Immunisation against infectious disease on contraindications to MMR vaccine use is also reviewed. It is important that false contraindications are not used by health professionals to wrongly deny children the protection provided by MMR vaccine.

Allied Health Personnel↗

Simultaneous administration of Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine with routine diphtheria-tetanus-pertussis and inactivated poliovirus vaccinations of childhood.

A Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) is capable of protecting infants against invasive H. influenzae diseases. Therefore it is very likely that it will be incorporated in routine vaccination schedules during the next few years. In order to test the suitability of simultaneous administration of PRP-D and other vaccines we administered it to 25 infants mixed with diphtheria-tetanus-pertussis vaccine at 3, 4 and 6 months and simultaneously, but in a separate syringe, with inactivated polio vaccine at 12 months. A comparison group of equal size received only diphtheria-tetanus-pertussis and inactivated poliovirus vaccines. The concentration of postvaccination antibodies to diphtheria toxoid was 0.411 IU/ml in the group that received PRP-D vs. 0.352 IU/ml in the comparison group, to tetanus toxoid 3.666 vs. 3.668 IU/ml and the neutralization titer to poliovirus type 1 was 370 vs. 320 units in the comparison group, to type 2 titer values were 230 vs. 270 units and to type 3, respectively, 210 vs. 290 units. Thus the seroresponse to antigens in routine vaccines was not affected by the presence of PRP-D in the vaccination schedule, and PRP-D can safely and effectively be included in the vaccination schedule of infancy.

Bacterial Vaccines↗

Induction of IL-2 and IFN-gamma in BALB/c mice immunised with subunit influenza A vaccine in combination with whole cell or acellular DTP vaccine.

Splenocytes from mice immunised with two doses of subunit influenza A/Beijing/353/89 vaccine mixed with whole cell DTP (wDTP), acellular DTP (aDTP) or PBS were collected 7 and 10 days after the second immunisation, and re-stimulated with subunit influenza vaccine or live virus in vitro. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were assayed in supernates from these cultures by an ELISA procedure. Splenocytes from mice given subunit influenza vaccine in wDTP produced greater than two-fold and greater than five-fold responses of IL-2 and IFN-gamma, respectively, compared with splenocytes from mice immunised with subunit vaccine alone. In contrast, the response of splenocytes from mice immunised with subunit vaccine in saline or aDTP was similar, significantly less than for vaccine in wDTP (p < 0.01) and only slightly greater than for controls (p < 0.05). The production of IL-2 and IFN-gamma by these spleen cells was not significantly different on days 7 and 10 post-immunisation. Previous reports have shown that wDTP and aDTP enhance the serum antibody response of mice to influenza vaccine, but wDTP enhanced the response 100-fold greater than aDTP, and induced greater IgG2a and IgG2b subclass antibody responses; this last result indicates a cell-mediated immune response to vaccine. The present studies confirm these earlier findings; furthermore, as the IL-2 and IFN-gamma responses of splenocytes are associated with Th-1 subset T-lymphocyte response, the findings indicate a cytotoxic T-cell response to immunisation. The results indicate that influenza vaccine combined with wDTP induced a cell-mediated response in mice, which could confer a more solid immunity to challenge virus infection.

Adjuvants, Immunologic↗

Comparative study and evaluation of further attenuated, live measles vaccines alone and in combination with mumps and rubella vaccines.

The further attenuated Enders (FAE) measles vaccine strain and the Edmonston B-Zagreb (EZ) measles vaccine strain were compared. In VERO-cells plaque sizes of FAE varied between 0.5 and 1 mm, those of EZ between 1 and 2 mm in diameter. The lots available in Switzerland during a 2 year period showed virus titers of 10(3.1) to 10(4.0) TCID50 per dose in the one vaccine (FAE) and of 10(3.1) to 10(4.5) TCID50 per dose in the other (EZ). Clinical investigations were performed with FAE and EZ monovalent and trivalent (measles + mumps + rubella) vaccine preparations. The virus titers of the vaccine lots used were 10(3.1) to 10(4.0) TCID50 per dose. The overall seroconversion rates of 96% to 100% indicate that both types of vaccine have comparable immunization properties. Stability tests demonstrated good stability of both the FAE and the EZ vaccines. Thus conservation at 37 degrees C was possible for 2 and 4 weeks, respectively, and at 41 degrees C for 6 and 6 days, respectively, without undue loss of live virus content (less than 1 log 10). Since the EZ vaccine is derived from human diploid cells, it is particularly suitable for the vaccination of persons with a history of allergy to avian proteins.

Animals↗

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine.

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.

Adult↗