Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine

BACKGROUND: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps, and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. AIM: To assess if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic "enterocolitis" theory. METHODS: We studied 109/58 infants, before and two and four weeks after immunisation with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). RESULTS: Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. CONCLUSIONS: The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis.     

Long-term persistence of mumps antibody after receipt of 2 measles-mumps-rubella (MMR) vaccinations and antibody response after a third MMR vaccination among a university population

BACKGROUND: High attack rates among vaccinated young adults reported during the 2006 mumps outbreak in the United States heightened concerns regarding mumps vaccine failure. METHODS: Serum specimens from university students and staff were tested for mumps immunoglobulin (Ig) G by enzyme immunoassay (EIA). A subset of participants vaccinated for < or =5 years and > or =15 years were tested by neutralizing antibody (NA) assay. Persons seronegative by EIA were offered a third dose of measles-mumps-rubella vaccine (MMR3), and serum specimens were obtained 7-10 days and 2-3 months after its administration. RESULTS: Overall, 94% (95% confidence interval [CI], 91%-96%) of the 440 participants were seropositive. No differences existed in seropositivity rates by sex, age, age at receipt of the second dose of MMR vaccine (MMR2), or time since receipt of MMR2 (P = .568). The geometric mean titer (GMT) of NA among persons vaccinated with MMR2 during the previous 1-5 years was 97 (95% CI, 64-148), whereas, among those vaccinated > or =15 years before blood collection, the GMT was 58 (95% CI, 44-76) (P = .065). After MMR3, 82% (14/17) and 91% (10/11) seroconverted in 7-10 days and 2-3 months, respectively. CONCLUSIONS: Lower levels of NA observed among persons who received MMR2 > or =15 years ago demonstrates antibody decay over time. MMR3 vaccination of most seronegative persons marked the capacity to mount an anamnestic response.     

Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine

To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16-B*44 haplotype was associated with lower levels of immunoglobulin G (IgG) antibody to both measles (P=.08) and mumps (P=.03) viral antigens. The A*26-Cw*12-B*38 haplotype was associated with higher cellular immune responses to measles (P=.02) and mumps (P=.01) vaccine viruses. Subjects with the class II DRB1*03-DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles virus (P=.01) and mumps virus (P=.006). The DRB1*15/16-DQB1*06-DPB1*03 haplotype was associated with high levels of IgG antibody to measles virus (P=.09) but low levels of IgG antibody to rubella virus (P=.02), whereas DRB1*04-DQB1*03-DPB1*03 was associated with high lymphoproliferative responses to both measles (P=.01) and rubella (P=.002) vaccine viruses. A*26-Cw*12-B*38 was associated with both mumps virus-specific humoral (P=.007) and cell-mediated (P=.01) immune responses after 2 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated with both lower rubella virus IgG antibody levels (P=.02) and higher rubella virus-specific lymphoproliferation (P=.002). Better characterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level.     

Immunization of healthy children with measles-mumps-rubella trivalent vaccine simultaneously given with varicella vaccine]

Trivalent vaccine, containing measles TD97, rubella TCRB-19 and mumps NK-M46 strains (MMR vaccine) was administered to a total of 116 healthy children of which 50 subjects were simultaneously injected with varicella vaccine in the opposite arm. The seroconversion rates for measles, mumps, rubella, and varicella in those who received both MMR and varicella vaccines (MMR + V group) were 100% (44/44), 91% (39/43), 100% (46/46) and 95% (39/41), respectively. And these rates were comparable to those in subjects receiving only MMR vaccine, namely 100% (64/64) for measles, 95% (57/62) for mumps, and 97% (58/60) for rubella. Fifty-eight children receiving MMR vaccine were seronegative to measles, mumps and rubella before vaccination, and 51 (88%) of them were found to be seropositive against all three viruses at 6 to 8 weeks after vaccination. Among the children injected with MMR and varicella vaccines, 36 subjects had no pre-antibodies to measles, mumps, rubella and varicella. Seroconversion in post-serum to all four viruses were found in 31 cases (86%). Clinical reactions observed in some vaccines were mild fever (17%) and exanthem (5%). There were no complications of lymphadenopathy, swelling in parotid regions, or meningitis. Our results indicate that simultaneous administration of MMR vaccine and varicella vaccine is a safe and effective method for immunizing children against these four infectious diseases.     

Safety and tolerability of ultra-Rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma

BackgroundThe safety and good tolerability of sublingual immunotherapy (SLIT) has already been proved in allergic patients, but only one study has investigated the occurrence of immediate adverse reactions in allergic patients after a 2-hour ultra-rush regimen of SLIT performed with a chemically modified extract (sublingual monomeric allergoid, Lais^®, Lofarma S.p.A., Milan). The objective of the present study was to evaluate the occurrence of immediate adverse reactions in allergic patients after a very fast (20 minutes) ultra-rush regimen of sublingual allergoid SLIT.Methods and resultsWe studied 105 patients: 28 children (20 male, mean age 13.3 ± 2.1 yr) and 77 adults (29 male, mean age 34.7 ± 9.9 years) with a history of intermittent/persistent rhinitis or intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the administration, every five minutes, of increasing doses of the sublingual allergoid SLIT. All patients tolerated the treatment very well. Only one patient out of 105 (0.9 %) had a mild local symptom (gastric pirosis) that occurred 30 minutes after the last initial dose and spontaneously disappeared as the treatment was continued.ConclusionsThese data show the excellent safety and tolerability profile of an ultra-rush SLIT regimen performed with a chemically modified extract, even when high doses were administered through an extremely short induction phase (20 minutes), thus confirming the previously reported results.     

A new measles mumps rubella (MMR) vaccine: a randomized comparative trial for assessing the reactogenicity and immunogenicity of three consecutive production lots and comparison with a widely used MMR vaccine in measles primed children.

OBJECTIVES: A multicenter, single-blind, randomized, controlled clinical study was conducted in healthy 15-18-month-old children in order to assess the immunogenicity and reactogenicity of three consecutive lots of a new measles- mumps-rubella (MMR) vaccine, GSK MMR. DESIGN: A total of 500 enrolled subjects were randomized into four groups to receive either a single dose of one of the three lots of GSK MMR (three groups--125 subjects in each group) or Merck MMR vaccine (125 subjects). Once clinical consistency had been demonstrated, the data were pooled and compared with the widely used Merck vaccine. Solicited local and general symptoms were recorded using diary cards, and antibody levels were determined using ELISA assays. RESULTS: No differences in the incidence of local and general symptoms or seroconversion rates were seen in the groups receiving different lots of GSK MMR. Compared with Merck MMR, there was a significantly lower incidence of local pain (P<0.001) and swelling (P=0.038) in infants receiving the GSK MMR vaccine. The incidences of all other solicited local and general symptoms were comparable between the two groups. No signs of suspected meningitis were reported. No serious adverse events were reported by the investigator to be related to vaccination. Equivalent seroconversion rates and postvaccination GMTs were observed in the groups receiving the two MMR vaccines. In conclusion, the new GSK MMR vaccine administered in measles-primed children demonstrated satisfactory immunogenicity and safety profiles as good as the Merck MMR vaccine.     

Safety and tolerability of ultra-rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma

BackgroundThe safety and good tolerability of sublingual immunotherapy (SLIT) has already been proved in allergic patients, but only one study has investigated the occurrence of immediate adverse reactions in allergic patients after a 2-hour ultra-rush regimen of SLIT performed with a chemically modified extract (sublingual monomeric allergoid, Lais^®, Lofarma S.p.A., Milan). The objective of the present study was to evaluate the occurrence of immediate adverse reactions in allergic patients after a very fast (20 minutes) ultra-rush regimen of sublingual allergoid SLIT.Methods and resultsWe studied 105 patients: 28 children (20 male, mean age 13.3 ± 2.1 yr) and 77 adults (29 male, mean age 34.7 ± 9.9 years) with a history of intermittent/persistent rhinitis or intermittent/ mild persistent asthma due to House Dust Mite (n = 56), Parietaria (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the administration, every five minutes, of increasing doses of the sublingual allergoid SLIT. All patients tolerated the treatment very well. Only one patient out of 105 (0.9 %) had a mild local symptoms (gastric pirosis) that occurred 30 minutes after the last initial dose and spontaneously disappeared as the treatment was continued.ConclusionsThese data show the excellent safety and tolerability profile of an ultra-rush SLIT regimen performed with a chemically modified extract, even when high doses were administered through an extremely short induction phase (20 minutes), thus confirming the previously reported results.     

Safety and immunogenicity of indigenous recombinant hepatitis B vaccine (Shanvac-B) in comparison with commercially available vaccine.

AIM: To assess the clinical safety, reactogenicity and immunogenicity of an indigenously developed recombinant hepatitis B vaccine (Shanvac-B; Shantha Biotechnics) and to compare it with another commercially available vaccine (Engerix-B, SmithKline Beecham) in healthy adults. METHODS: 120 healthy adults randomLy received 20 micrograms of either Engerix-B (Group A; n = 61) or Shanvac-B (Group B; n = 59) in 0, 1, 2 months schedule. Anti HBs was assessed using commercially available AUSAB kits (Abbott Laboratories) one month after each dose. RESULTS: Protective seroconversion rates after first, second and third dose were 10%, 62.7% and 91.4%, respectively in Group A and 22.4%, 68.9% and 96.4% in Group B, respectively. The geometric mean titer (GMT) after the third dose was significantly high in Group B (419 mIU/mL) than in Group A (140 mIU/mL; p < 0.001). The GMT was significantly higher in women in both the groups. The indigenous vaccine was found to be clinically safe and well tolerated without significant side effects. CONCLUSION: The recombinant hepatitis B vaccine (Shanvac-B) developed in India is safe, well tolerated, and highly immunogenic, with high seroconversion and GMT response.     

Aseptic meningitis in a large MMR vaccine campaign (590,609 people) in Curitiba, Paraná, Brazil, 1998.

The aseptic meningitis after Measles-Mumps-Rubella vaccine (MMR) is a well recognized complication, and different incidences have been observed in several studies. We retrospectively analyzed forty cases of aseptic meningitis, during a large public immunization campaign (1998) in Curitiba, Southern Brazil (590,609 people), admitted in our Service. The vaccine utilized was Leningrad-3-Zagreb mumps strain, Edmonston-Zagreb measles strain, and RA 27#3 rubella strain. In all county, a total number of 87 cases were reported, resulting in a incidence of 1.7 cases per 10,000 given doses. The mean age was 23.7 +/- 12.8 years. The female:male ratio was 1.35:1. Severe headache with meningismus (92.5%), fever (87.5%), nausea/vomiting (82.5%) were the most common clinical findings. Three cases (7.5%) developed mild mumps. All patients underwent cerebrospinal fluid (CSF) tap with the following findings: mononuclear pleocytosis from 100 to 500 cells/mm(3) in 17 cases (42.5%; 257.5 +/- 260.6 cells/mm3); increased protein 28 cases (67.5%; 92.1 +/- 76.9 mg/dL); glucose was normal in all cases (56.8 +/- 11.2 mg/dL) except in 4 (10%) cases, which presented less than 44 mg/dL. All serological tests (latex to bacterial meningitis, Cryptococcus, cysticercosis, VDRL) and bacteriological cultures were negative. Virus identification were also negative in 8 samples. None of the patients had neurological deficits or related symptoms after one year of onset. We believe the benefit of vaccination clearly outweighs the incidence of benign vaccine-associated meningitis.     

Safety and response to influenza vaccine in patients with systemic-onset juvenile idiopathic arthritis receiving tocilizumab

Objective

We investigated the safety and efficacy of administering influenza vaccines to patients with systemic-onset juvenile idiopathic arthritis (sJIA) treated with tocilizumab.

Patients and methods

The subjects were 27 sJIA patients treated with tocilizumab and 17 healthy age- and sex-matched volunteers. Serum samples were collected prior to and 4–7 weeks after vaccination. Hemagglutination inhibition values of the vaccine were taken as the antibody titers. The duration of tocilizumab administration and the daily doses of prednisolone per unit body weight were analyzed to identify factors affecting the responses of the sJIA patients to influenza vaccination. We questioned all the subjects about whether they had contracted influenza and whether they had had adverse reactions to the influenza vaccination. We compared steroid doses in sJIA patients before and after vaccination to document any worsening of the underlying disease.

Results

The efficacy of influenza vaccination did not differ significantly between the sJIA group and the healthy controls. The duration of tocilizumab administration did not affect the response of the sJIA patients to the influenza vaccination. None of the sJIA patients experienced either severe adverse reactions or disease exacerbation after the influenza vaccination.

Conclusion

We found that sJIA patients treated with tocilizumab could be effectively and safely immunized with the influenza vaccine.     

Continuous low-dose subcutaneous desferrioxamine (DFO) to prevent allergic manifestations in patients with iron overload

 In some patients compliance to subcutaneous desferrioxamine therapy is reduced because of allergic symptoms. Effective drug desensitization consists of bringing patients to tolerate the same mode of administration. We evaluated three thalassemic patients with severe allergies to desferrioxamine. Each patient received weekly three prefilled infusors with desferrioxamine 4 g/48 m1/48 h for s.c. therapy. Follow-up was performed for 12 consecutive weeks. During follow-up no allergic events were noted. The s-ferritin levels decreased from 2583 μg/l±485 to 1916 μg/l±275 (mean decrease 25.8%, p=0.038). Compliance to the infusional system was excellent. Our results show that continuous infusion of desferrioxamine using a new infusional delivery system is effective in preventing allergic reactions and in reducing iron overload. Received: 12 June 1996 / Accepted: 3 September 1996     

High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration

To test the hypothesis that allergy to desferrioxamine is not an immunologic mechanism, but arises from a local effect on the dermal mast cell, we have treated four patients who were not receiving chelation therapy because of hypersensitivity to standard subcutaneous (SC) therapy, with high-dose desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central venous access ports implanted on the anterior chest wall. The fourth patient had the therapy delivered by the peripheral vein route. All patients had the drug delivered via an elastomeric infusor. Intravenous therapy was successful for all patients. During one year of therapy no local or systemic allergic manifestations were noted. In addition, no impairment of hearing or vision or any catheter complications were reported. A very high level of patient compliance to the therapy resulted in dramatically decreased iron stores and ferritin levels (2,759 ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all patients. The absence of allergic episodes in this patient group after 1 year of IV therapy would strongly support the hypothesis that SC DFO allergy is related to a direct effect on dermal mast cells and is not an immunological reaction. This study suggests that patients with severe allergy to SC DFO can therefore safely receive their chelation therapy via the IV route. © 1996 Wiley-Liss, Inc.     

变应原疫苗免疫治疗对过敏性支气管哮喘合并鼻炎的疗效分析

目的评估标准化变应原疫苗免疫治疗（allergeni mmunotherapy,AIT）对过敏性哮喘合并鼻炎患者的近期疗效。方法设计调查问卷,对我院门诊接受标准化变应原疫苗-安脱达（Alutard（SQ）AIT治疗的39例过敏性哮喘合并鼻炎患者进行问卷调查,应用哮喘控制水平分级和哮喘控制测试（ACT）评分评价哮喘的疾病控制水平,应用鼻炎病情评分（RCT）评价过敏性鼻炎的控制情况。结果 39例患者治疗前后的哮喘控制水平分级（Z=-7.235,P〈0.05）、ACT评分（t=16.533,P〈0.05）、RCT评分（t=16.650,P〈0.05）、情绪（χ2=34.873,P〈0.05）等均有较大程度的改善。结论标准化AIT治疗能明显改善过敏性哮喘合并鼻炎患者的临床症状。     

变应原疫苗免疫治疗对过敏性支气管哮喘合并鼻炎的疗效分析

目的 评估标准化变应原疫苗免疫治疗(allergen immunotherapy,AIT)对过敏性哮喘合并鼻炎患者的近期疗效.方法设计调查问卷,对我院门诊接受标准化变应原疫苗-安脱达(Alutard(R)SQ)AIT治疗的39例过敏性哮喘合并鼻炎患者进行问卷调查,应用哮喘控制水平分级和哮喘控制测试(ACT)评分评价哮喘...     

Safety and efficacy in two-dose vaccination using measles and rubella combined (MR) vaccine

Measles and rubella combined (MR) vaccine and two-dose-vaccination have been used in Japan since 2006. only children undergoing monovalent measles and rubella vaccination undergo a second vaccination. We intend to administer MR vaccine twice to Japanese children from 2011, so studied the safety and efficacy of two-dose MR vaccination. Subjects were 75 pre school children undergoing MR vaccine manufactured by Biken at one year old in a clinical trial. Children were observed for adverse events for 28 days after the second MR vaccination. Efficacy was determined by measuring antibodies for measles and rubella before and after (six to eight weeks later) the second vaccination. Results showed that fever frequency decreased significantly from 27.3% to 14.9% (p < 0.05), and eruption decreased from 12.2% to 6.8% from the first to the second vaccination, whereas, the frequency of redness and swelling at the inoculation site increased from 7.3% to 10.8% and 2.9% to 8.1%. Differences are not statistically significant. Measles antibody titer determined by NT assay and rubella antibody titer measured by HI assay increased significantly from prevaccination to postvaccination (p < 0.0001). Measles antibodies measured by NT and EIA assays and rubella antibody measured by HI assay turned positive in all subjects after the second MR vaccination. In conclusion, two-dose MR vaccination should be safe and effective in eliminating measles and rubella in Japan.     

Development of influenza A(H7N9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs

Background

The emergence of avian influenza A(H7N9) virus in poultry causing zoonotic human infections was reported on March 31, 2013. Development of A(H7N9) candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated without delay. Candidate vaccine viruses were derived by reverse genetics using the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, especially in a pandemic situation.

Methods

Two CVVs derived by reverse genetics were serially passaged in embryonated eggs to improve the hemagglutinin (HA) antigen yield. The total viral protein and HA antigen yields of six egg-passaged CVVs were determined by the BCA assay and isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were antigenically characterized by hemagglutination inhibition (HI) assays with ferret antisera.

Results

Improvement of total viral protein yield was observed for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately a twofold increase in yield of several egg-passaged viruses as compared to that of the parental CVV. Several different amino acid substitutions were identified in the HA of all viruses after serial passage. However, HI tests indicated that the antigenic properties of two CVVs remained unchanged.

Conclusions

If influenza A(H7N9) viruses were to acquire sustained human-to-human transmissibility, the improved HA yield of the egg-passaged CVVs generated in this study could expedite vaccine manufacturing for pandemic mitigation.