Israel Medical Association Journal

Background: The evaluation of influenza vaccine activity and potency are based on the immune response to hemagglutinin, and protection is indicated when a ≥ 1:40 titer of hemagglutination inhibition serum antibody is present. Neuraminidase, the second surface glycoprotein, may also have a role in protection, but little information on the immunologic response to this component is available.

Objectives: To determine whether any response to neuraminidase is evoked by intranasal immunization with a novel, whole, inactivated anti-influenza vaccine.

Methods: This study was part of a more comprehensive study of mucosal and serum immune response to this vaccine. Fifty-four young adults were immunized intranasally, 9 intramuscularly and 18 received a placebo. Twenty-three elderly people were immunized intramuscularly, and 21 elderly and 17 children were immunized intranasally. Serum and nasal antibodies to antigens N1 and N2 were determined by the lectin neuraminidase test.

Results: Serum response following intranasal vaccination was lower than after intramuscular vaccination, and ranged from 21.4 to 35.3% and 33.3 to 64.7% following intranasal vaccination and 52.2 to 77.8% and 47.8 to 88.9% after intramuscular vaccination, to N1 and N2 respectively. Nasal antibody response was low and was found only after intranasal vaccination, and response to N2 was better than to the N1 antigen.

Conclusions: It may be beneficial if future vaccines would include competent hemagglutinin and neuraminidase, which would afford a higher level of protection.
 

Background: Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality.

Objective: To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000–2001 influenza season.

Methods: A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of “Maccabi Health Care Services” – the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes.

Results: Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups.

Conclusions: In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.

Background: Previous data showed that new recombi­nant hepatitis B virus vaccine, which contains the S-protein component of the HBV surface together with the Pre-S₁ and Pre-S₂, is considerably more immunogenic than a second-generation recombinant I-IBV vaccine.

Objectives:To compare the immunogenicity and safety of a novel recombinant HBV vaccine S1, Pre-S₁ and Pre-S₂ protein components of the hepatitis B surface antigen - Bio­TM

Hep^TM 10 לg dose, to a licensed vaccine containing only the S-protein component - Engerix-B, 20 לg dose.

Methods: A prospective randomized study included 524 adults - 260 in the Bio-Hep group and 264 in the Engerix-B group. Both vaccines were administered in a three-dose regimen given at 0, 1 and 6 months, and adverse events were recorded on a diary card 5 days after each vaccination. lmmunogenicity was tested by measuring anti-hepatitis B surface antibody.

Results: One month after the third injection, 98% of the BioHep^TM subjects were found to be seroprotected vs. 85.1% of the Engerix-B group. In addition, the geometric mean titers were 2,203 mlU/ml and 326 mlU/ml in the Bio-Hep-B and Engerix-B groups respectively. An immunogenic advantage of Bio-Hep-B was suggested by the rapid onset of antibody response - 66.5% were seroconverted one month after the first injection as compared to 19.3% in the Engerix-B group. No unexpected adverse events were observed, and the recorded events were mild in both groups.

Conclusions: BioHepTM, a novel recombinant HBV vaccine containing 5, Pre-S₁ and Pre-S₂ protein components. at a lower dose, is safe and more immunogenic than the conventional HBV vaccine that contains only S protein.

Background: High dose interleukin-2 therapy, adminis­tered in bolus, is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma.

Objectives: To present our experience using this mode of therapy in 21 patients with metastatic melanoma.

Materials and Methods: The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years (range 29-63). Their metastatic disease was present in all extracranial sites, dermal and sub-dermal metastases being the most common (15 patients had at least one site, in addition to other locations of metastases). Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between. Radiological and physical evaluation was performed 6-8 weeks after the first course. If a response was achieved a second course of therapy was given. Patients received up to 14 planned doses of IL-2 in each week, 720,000 lU/kg of IL-2 per dose iv. in 15 minutes. All treatments were given in the surgical ward, and only one patient was hospitalized in the intensive care unit.

Results: Of the 21 patients, one had a complete response that has lasted for 17 months and 5 patients had a partial response (range 3 months to 3 years). One patient died during treatment, and one patient who refused further treatment because of no response died a few days after completion of treatment. Prior to therapy three of the responders had received autologous vaccines with good immunological response (P=0.115). Toxic side effects were significant, but they were treated successfully with no residual damage.

Conclusions: High dose IL-2 can be administered safely in a surgical department. The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients. To improve response rates, a combination of auto­logous vaccines prior to high dose IL-2 may be recommended.

Methods: The study was conducted in the three general hospitals in Haifa City, and in five nursing homes in the Haifa subdistrict. Self-administered questionnaires were distributed to 1,014 employees of whom 71% were females, 34% were nurses, 27% were physicians and 28% were non-professional workers.

Results: The crude response rate was 66%. Response rates were higher in females (71%) than in males (49%), in nurses (70%) than in physicians (43%), and in staff of internal and pediatric departments than in workers of surgery departments and emergency rooms. The overall vaccination rate among the respondents was 11%, which was higher among males (15%) than among females (10%). No significant relationship between vaccination rate and age, occupation and department was found. The vaccination rate among employees with chronic illness was very low (7%). Influenza vaccine was actively recommended to 29% of the employees. The main reasons for non-compliance were low awareness of the severity of the disease and of the vaccine's efficacy and safety, and unavailability of the vaccine within the workplace.

Conclusions: Educational efforts and offering the vaccine at the workplace at no cost are the most important measures for raising influenza vaccination rates.

Background: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine.

Objectives: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity.

Methods: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants.

Results: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex.

Conclusions: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.

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MMR= measles-mumps-rubella

Background: DHEAS, the most abundant steroid secreted by the adrenal cortex, is suggested to have an important role in the development of immune reaction by activating T cell function and increasing antibody response, and has been tried as a vaccine adjuvant in elderly people.

Objectives: We examined the correlation between endogenous DHEAS and antibody response in the neonatal period by comparing the serum DHEAS levels with the amount of antibody response against hepatitis B vaccination in neonates.

Methods: Vaccine was administered to 12 healthy infants within 24 hours of birth (day 0), and blood specimens were obtained on days 0 and 30 for determination of anti-hepatitis B surface antibody concentration and DHEAS levels.

Results: DHEAS levels varied widely (range 0.38-3.70 μg/ml, mean±SD 2.14±0.98). While we could identify two groups of patients - those with high DHEAS levels (2.90±0.56) and those with lower levels (1.30±0.56) - there was no correlation between DHEAS levels and the antibody response to hepatitis B vaccine (γ=-0.05).

Conclusions: In neonates, antibody response to hepatitis B vaccine does not correlate with DHEAS serum levels. These results do not support the usage of DHEAS as a vaccine adjuvant in neonates.

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DHEAS= dehydepiandrosterone sulphate