Prior Immunization Research Articles

Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge.

Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

Self-collected buccal swabs and rapid, real-time PCR during a large measles outbreak in Wales: Evidence for the protective effect of prior MMR immunisation

BackgroundWe describe the laboratory response to a large measles outbreak that occurred during 2012–2013 centred in mid and west Wales, UK. ObjectivesTo demonstrate the impact of rapid measles testing on the management of a large outbreak, to show the complex molecular epidemiology and determine the role of previous MMR immunisation on a large cohort of exposed people. Study DesignResults from oral fluid antibody testing and self-collected buccal swabs tested by real-time PCR were reconciled and analysed to determine level of agreement and to calculate MMR vaccine efficacy during the outbreak. ResultsDuring the outbreak 1435 notifications of measles were received from across Wales. Samples were received from 70% of notified cases with a positivity rate of 56% within the outbreak compared to 15% for the rest of Wales. Measles RNA was detected in 53 cases with previous history of MMR immunisation, but viral loads were lower than those detected in unimmunised cases. The molecular epidemiology showed at least two distinct D8 strains of measles virus were introduced into Wales along with a separate introduction of a B3 strain outside the outbreak area. ConclusionMolecular testing of all notified measles cases offers the most rapid way of confirming the introduction of measles into a population potentially before secondary transmission has already occurred. The outbreak data confirms the protective effect of the MMR vaccine with vaccine efficacy calculated at 96% for one dose and 99% for two doses supporting the WHO recommendations for a two dose MMR immunisation schedule.

The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs.

The reduction of brain amyloid beta (Aβ) peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ 40, and Aβ 42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ 40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.

Zinc supplementation fails to increase the immunogenicity of oral poliovirus vaccine: A randomized controlled trial

BackgroundPolio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV). ObjectiveTo assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV). MethodsA double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0–14 days). Subjects were assigned to either receive 10mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status. ResultsOverall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60μg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p<0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3. ConclusionsThere was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels.

Factors associated with maternal influenza immunization decision-making

Objective: We examined pregnant women's intention to obtain the seasonal influenza vaccine via a randomized controlled study examining the effects of immunization history, message exposure, and sociodemographic correlates.Methods: Pregnant women ages 18–50 participated in a randomized message framing study from September 2011 through May 2012. Venue-based sampling was used to recruit racial and ethnic minority women throughout Atlanta, Georgia. Key outcomes were evaluated using bivariate and multivariate analyses.Results: History of influenza immunization was positively associated with intent to immunize during pregnancy [OR = 2.31, 90%CI: (1.06, 5.00)]. Significant correlates of intention to immunize included perceived susceptibility to influenza during pregnancy [OR = 3.8, 90% CI: (1.75, 8.36)] and vaccine efficacy [OR = 10.53, 90% CI: (4.34, 25.50)]. Single message exposure did not influence a woman's intent to vaccinate.Conclusions: Prior immunization, perceived flu susceptibility and perceived vaccine effectiveness promoted immunization intent among this population of pregnant minority women. Vaccine efficacy and disease susceptibility are critical to promoting immunization among women with no history of seasonal influenza immunization, while those who received the vaccine are likely to do so again. These findings provide evidence for the promotion of repeated exposure to vaccine messages emphasizing vaccine efficacy, normative support, and susceptibility to influenza.

Nasal sensitization with ragweed pollen induces local-allergic-rhinitis-like symptoms in mice.

Recently, the concept of local allergic rhinitis (LAR) was established, namely rhinitis symptoms with local IgE production and negative serum antigen-specific IgE. However, the natural course of LAR development and the disease pathogenesis is poorly understood. This study investigated the pathophysiology of mice with allergic rhinitis that initially sensitized with ragweed pollen through the nasal route. Mice were nasally administrated ragweed pollen over consecutive days without prior systemic immunization of the allergen. Serial nasal sensitization of ragweed pollen induced an allergen-specific increase in sneezing, eosinophilic infiltration, and the production of local IgE by day 7, but serum antigen-specific IgE was not detected. Th2 cells accumulated in nose and cervical lymph nodes as early as day 3. These symptoms are characteristic of human LAR. Continual nasal exposure of ragweed pollen for 3 weeks resulted in the onset of classical AR with systemic atopy and adversely affected lung inflammation when the allergen was instilled into the lung. Fcer1a −/− mice were defective in sneezing but developed normal eosinophilic infiltration. Contrary, Rag2 −/− mice were defective in both sneezing and eosinophilic infiltration, suggesting that T cells play a central role in the pathogenesis of the disease. These observations demonstrate nasal allergen sensitization to non-atopic individuals can induce LAR. Because local Th2 cell accumulation is the first sign and Th2 cells have a central role in the disease, a T-cell-based approach may aid the diagnosis and treatment of LAR.

The CD4 T cell response to respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) can induce severe lower respiratory tract infections in infants and is the leading cause of bronchiolitis in children worldwide. RSV-induced inflammation is believed to contribute substantially to the severity of disease. T helper (Th)2-, Th9-, and Th17-related cytokines are all observed in infants hospitalized following a severe RSV infection. These cytokines cause an influx of inflammatory cells, resulting in mucus production and reduced lung function. Consistent with the data from RSV-infected infants, CD4 T cell production of Interleukin (IL)-9, IL-13, and IL-17 has all been shown to contribute to RSV-induced disease in a murine model of RSV infection. Conversely, murine studies indicate that the combined actions of regulatory factors such as CD4 regulatory T cells and IL-10 inhibit the inflammatory cytokine response and limit RSV-induced disease. In support of this, IL-10 polymorphisms are associated with susceptibility to severe disease in infants. Insufficient regulation and excess inflammation not only impact disease following primary RSV infection it can also have a major impact following vaccination. Prior immunization with a formalin-inactivated (FI-RSV) vaccine resulted in enhanced disease in infants following a natural RSV infection. A Th2 CD4 T cell response has been implicated to be a major contributor in mediating vaccine-enhanced disease. Thus, future RSV vaccines must induce a balanced CD4 T cell response in order to facilitate viral clearance while inducing proper regulation of the immune response.

Effects of β-conglycinin on growth performance, immunoglobulins and intestinal mucosal morphology in piglets

One of the main causes of allergic reactions in young animals is β-conglycinin, an antigenic glycoprotein found in soya beans. Therefore, the objective of the study was to investigate the effects of a prior immunisation with β-conglycinin on growth performance, serum immunoglobulin levels and intestinal histology in piglets. Forty piglets (7 d of age) were randomly divided into four groups of ten piglets each. Piglets of Groups Im and Im+S were immunised twice by hypodermic injection with β-conglycinin at 500 μg/kg body weight (BW) at day 7 and 21 of age. At day 23, Groups Im+S and S were intramuscularly injected with 5000 μg β-conglycinin per kg BW. The piglets of Group C received a physiological saline solution by hypodermic injection. All piglets were weaned at the age of 23 d and blood samples were taken on days 7, 21 and 35. At the end of the trial, five piglets per group were slaughtered and the intestine was collected for evaluating mucosal histology. Compared to Group C, in Group S the average daily gain (ADG), feed intake and gain:feed ratio were decreased (p < 0.01), and serum levels of IgG and IgE were increased (p < 0.01). Furthermore, in this group the structure of duodenal and jejunal mucosa was severely damaged. But in Groups Im and Im+S the ADG was increased (p < 0.05), serum IgE levels were decreased (p < 0.01) and the intestinal mucosa was not damaged. The results suggest that prior immunisation with β-conglycinin can increase ADG and serum IgG levels and decrease serum IgE levels. Therefore, this method is also potentially able to protect the structural integrity of the intestinal mucosal epithelia and alleviate allergic reactions in piglets.

Using the Nonhuman Primate Model of HCMV to Guide Vaccine Development

The natural history of human cytomegalovirus (HCMV) is inextricably associated with mucosal surfaces. The vast preponderance of primary infections occur following mucosal exposure to infectious virions, and the high seroprevalence of HCMV throughout the world is due to long-term excretion of HCMV in bodily fluids from multiple mucosal sites. Accumulating evidence presents a model where the earliest virus-host interactions following infection dictate the long-term pattern of infection, alter innate immune responses that skew adaptive responses to enable persistence within an immune host, and are essential for reinfection of a host with prior immunity. HCMV has evolved a complex repertoire of viral functions fine-tuned to manipulate the immune environment both locally at the sites of infection and systemically within an infected host. Collectively, viral immune modulation represents a significant impediment for an HCMV vaccine. As HCMV can disseminate beyond mucosal surfaces to reinfect immune hosts, it may not matter whether prior immunity results from prior infection or immunization. A better understanding of the earliest virus-hosts interactions at mucosal surfaces may identify elements of the viral proteome that are especially susceptible to vaccine-mediated disruption and prevent challenge virus from disseminating to distal sites, particularly the maternal-fetal interface.

TETANUS;

Background: Tetanus still remains a major public health problem in Pakistan like in most other developing countries, with ahigh morbidity and mortality. Objectives: To study the demographic profile the clinical profile, the outcome of the tetanus patients andeffectiveness of tetanus immunization coverage in district Faisalabad. Design: Retrospective record based study. Place and Duration:Surgical unit-5 DHQ Hospital, Faisalabad from January 2010 to December 2012. Subjects and Methods: All data of 198 patients oftetanus of any age and sex, diagnosed clinically was collected, compiled and analyzed from the Medical Records Department of theHospital. Results: Out of 198 patients of tetanus,138(69.7%) were males and 60(30.3%) were females. Their ages ranged from 1 to 85years with a mean and a standard deviation respectively of 29.36 and 17.48 years.162 (81.8%) were from rural and36(18.2%) were fromurban areas. 47(23.7%) patients were having prior immunization and151(76.3%) were not immunized. The most common presentingsymptoms were trismus (47.5%), body stiffness(24.2%),fits(19.2%) and respiratory distress(9.1%). 23(11.6%) patients were havingmild disease,71(35.9%) patients were having moderate disease,71(35.9%) patients were having severe disease and 33(16.7%) werehaving very severe disease. Overall mortality rate was 41.4%. Respiratory failure was the most common cause of death and there wasstatistically significant association between mortality and increasing grades of disease. Conclusions: By making expanded programmeof immunization(EPI) more effective and removing flaws from out-dated vaccination through incomplete vaccination. By improvingawareness in public and complete vaccination through EPI program, we can reduce the incidence of tetanus.

Safety Of Splenectomy In Hematological Diseases

Introduction Splenectomy is a diagnostic tool and an option of treatment for some diseases. After splenectomy, the risk of infection is not clear in adult populations, therefore designing and implementing the best prevention and management strategys is of upmost importance. Splenectomized patients also have an increased risk of venous thromboembolism. Perioperative anticoagulant prophylaxis with subcutaneous heparin should be administered to all patients and in high risk patients prolonged anticoagulant prophylaxis (at least 4 weeks) should be used. There is not much information about infection and thromboembolic risk after splenectomy in hematological patients. Aims To evaluate the efficacy and safety of splenectomy in adult patients with hematological diseases. Methods Splenectomies performed in our hospital between March 2003 and February 2013 in adults with hematological disease were reviewed. Diagnosis, age at time of splenectomy, cardiovascular risk factors (CVRF), immunosuppressive therapy, type of surgery, immunization against encapsulated bacteria, antibiotic and thromboembolic prophylaxis, serious infections and thromboembolic events were considered. Severe infection was defined as one that required emergency consultation or admission and antibiotic, antiviral and antifungal treatment. Results A total of 65 splenectomies were performed in patients with hematologic disorders. Underlying diseases were primary immune thrombocytopenia (ITP) in 24 patients, splenic marginal zone lymphoma in 13, other lymphoproliferative disorders in 13, microspherocytosis in 10, Evans syndrome (ES) in 2 and immune hemolytic anemia (AIHA) in 2. The median age at splenectomy was 51 years old (r, 18-78). A laparoscopic procedure was performed in 83% of patients, with a median admission duration of 5 days (r, 3-33) vs 10 days (r, 5-12) for laparotomic procedures. All patients received prior immunization although in two cases the administration was postoperative. Twenty eight percent of subjects received steroids for ≥ 2 months prior to surgery and 12.5 % rituximab. Fifty percent of patients suffered a severe infection after a median of 16 months (r, 0-84 months), 75% of which received antibiotic prophylaxis. There was no difference in the incidence of infection between different hematological diagnoses. The most frequent locations were respiratory and urinary infections, 27.1% and 18.6% respectively. The most commonly isolated germs were Candida, E.Coli, P. Aeruginosa, VEB and P.Mirabillis. Six patients developed thrombotic events, after a median of 10 days (r, 1-93 days). Of these, 50% had not received thromboembolic prophylaxis. The locations were pulmonary thromboembolism (1), subclavian vein thrombosis (2), portal vein thrombosis (1) and stroke (2). We found no significant differences in the platelet count and cardiovascular risk factors in subjects with and without thromboembolic events. There were 8 (12.3%) cases of exitus, 3 of which were due to infectious events (2 septic shock, 1 respiratory infection). After a median follow-up of 35 months (r, 1-106 months) 100% of AIHA and ES and 82.6% of PTI are in remission. Conclusions In our experience splenectomy is a safe and effective procedure and continues to have an important role in the management of certain hematological disorders. Due to sample size, it is difficult to draw conclusions on the impact of antibiotic prophylaxis maintenance, although, as in our series the risk of infection is present until 84 months after surgery, we believe prophylaxis should be maintained for at least 3 to 5 years. Furthermore, our results support the recommendations provided in the literature on thromboprophylaxis for at least 4 weeks after surgery. Disclosures: No relevant conflicts of interest to declare.

Development of specific scFv antibodies to detect neurocysticercosis antigens and potential applications in immunodiagnosis

We have shown previously that detection of circulating antibodies against mimotopes selected by phage display were useful in neurocysticercosis diagnosis. However, circulating antigens may also be useful in patients’ clinical follow-up. Therefore, we aimed to select novel combinatorial antibodies, single-chain variable fragment (scFv), which can be used for specific antigens with pre-defined affinity and specificity without prior immunization. A phage scFv antibody library was selected against Taenia solium mimotopes displayed on phages coupled in beads and total saline extract of T. solium metacestodes (S) immobilized on microtiter plate wells. After two rounds of selection, 96 phage clones were evolved and validated against each target by enzyme linked immunosorbent assay (ELISA), and dot-blot, and three specific antibodies (B6, G10 and A4) were further characterized by sequencing and indirect immunofluorescence (IFI) assays. IFI revealed tegument staining for the B6, while the others showed a non-uniform staining in the whole parasite. The selected scFvs were used to capture their antigen targets that were elucidated through mass spectrometry, and used for antibody detection in NC patients’ sera by ELISA, which achieved sensitivities greater than 97% and specificities above 95%. We have successfully developed scFv antibodies against important mimotopes used in NC diagnosis, and can be further explored to detect circulating antigens for clinical follow-up of patients with NC. Our strategy also highlighted the possibility of using this combinatorial approach to select, capture and characterize specific antigens to better understand this intriguing parasite infection and disease evolution.

Exosomes carrying mycobacterial antigens can protect mice against Mycobacterium tuberculosis infection

Approximately 2 billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), and an estimated 1.5 million individuals die annually from TB. Presently, Mycobacterium bovis BCG remains the only licensed TB vaccine; however, previous studies suggest its protective efficacy wanes over time and fails in preventing pulmonary TB. Therefore, a safe and effective vaccine is urgently required to replace BCG or boost BCG immunizations. Our previous studies revealed that mycobacterial proteins are released via exosomes from macrophages infected with M. tuberculosis or pulsed with M. tuberculosis culture filtrate proteins (CFP). In the present study, exosomes purified from macrophages treated with M. tuberculosis CFP were found to induce antigen‐specific IFN‐γ and IL‐2‐expressing CD4+ and CD8+ T cells. In exosome‐vaccinated mice, there was a similar TH1 immune response but a more limited TH2 response compared to BCG‐vaccinated mice. Using a low‐dose M. tuberculosis mouse aerosol infection model, exosomes from CFP‐treated macrophages were found to both prime a protective immune response as well as boost prior BCG immunization. The protection was equal to or superior to BCG. In conclusion, our findings suggest that exosomes might serve as a novel cell‐free vaccine against an M. tuberculosis infection.

Olfactory Bulb and Hypothalamic Acute-Phase Responses to Influenza Virus: Effects of Immunization

Background: Within hours of intranasal challenge, mouse-adapted H1N1 A/Puerto Rico/8/34 (PR8) influenza genomic RNA is found in the olfactory bulb (OB) and OB pro-inflammatory cytokines are up-regulated. Severing the olfactory tract delays the acute-phase response (APR) and the APR is attenuated by immunization. Objectives: To determine if immunization affects OB localization of influenza or the molecular brain mechanisms regulating APR. Methods: Male mice were immunized with PR8 influenza, then OB viral RNA, APR, and influenza-related cytokine responses were determined after homologous viral challenge. Results: Immunization did not prevent influenza OB viral invasion within 24 h of viral challenge. However, it greatly attenuated OB viral RNA 6 days after viral challenge and the APR including hypothermia and body weight loss responses. Within the OB, 24 h after influenza challenge, prior immunization blocked virus-induced up-regulation of toll-like receptor 7 and interferon (IFN) γ mRNAs. At this time, hypothalamic (HT) growth hormone-releasing hormone receptor and tumor necrosis factor-α mRNAs were greatly enhanced in immunized but not in positive control mice. By 6 days after viral challenge, OB and HT mRNAs returned towards baseline values. In the lung, mRNA up-regulation was greater than that in the brain and maximized 6 days after challenge. Lung IFNγ mRNA decreased at 24 h but increased 6 days after challenge in the positive compared to negative controls. Immunization prevented the up-regulation of most of the flu-related mRNAs measured in lungs. Conclusion: Collectively, these data suggest a role for OB and HT involvement in immunization protection against influenza infection.

Acute Measles Encephalitis in Partially Vaccinated Adults

BackgroundThe pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam.Methods and FindingsFifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008–2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/− IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier). AME patients had low CD4 (218/µl, p = 0.029) and CD8 (200/µl, p = 0.012) T-cell counts compared to controls.ConclusionYoung adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be assessed in randomized clinical trials.

Cost-effectiveness analysis of MMR immunization in health care workers

Assessment of measles, mumps and rubella (MMR) status is an essential part of occupational health clearance for new health care workers (HCWs). At the time of this study the policy at Sheffield Occupational Health Service (SOHS) was to perform serological testing of HCWs without evidence of previous immunization prior to MMR vaccination. To identify the cost implications of changing policy to offer vaccination without prior serological testing to HCWs without evidence of previous immunization. A retrospective cohort analysis of all MMR serological results from individuals attending SOHS for pre-placement assessment between 1 April 2010 and 31 March 2012. Seven thousand five hundred and sixty-nine individuals attended SOHS for pre-placement screening. Of these, 52% (3921) had no evidence of prior vaccination to at least one MMR disease and underwent serological testing. Thirty-three per cent (1204) of these HCWs were sero-negative to at least one condition requiring vaccination. With the suggested change in policy, our data indicate a cost-saving of over £105 000 per year may currently be achieved at SOHS. Our findings highlight significant savings through offering vaccination without prior serology for HCWs with no evidence of prior immunization to MMR. An awareness of costs associated with serology, vaccination and staff clinics, as well as the wider impact of population vaccination campaigns, are important factors determining the most cost-effective strategy in this area.

Anti-leucocyte antibodies in platelet apheresis donors with and without prior immunizing events: implications for TRALI prevention

Transfusion-related acute lung injury (TRALI) prevention strategies in platelet (PLT) apheresis donors focus on identifying antileucocyte antibody-positive donors. The use of microbead based assays for screening purposes is hampered by the lack of a consensus cut-off for TRALI prevention and the undefined role of anti-leucocyte antibodies in never-alloexposed donors. This study evaluated anti-leucocyte antibody assays in PLT apheresis donors with and without prior immunizing events with special focus on microbead assay cut-offs, antibody specificities and their potential significance in never-alloexposed donors. Blood samples of male and female PLT apheresis donors with and without history of prior immunization were tested for anti-leucocyte antibodies. Of 262 female and 118 male PLT apheresis donors, 37·4% had prior immunizing events. Fifty-eight of 238 (24·4%) donors without prior immunizing event had anti-HLA antibodies confirmed in microbead single antigen assay (mean fluorescence intensity (MFI) >500). Even with a cut-off MFI >3000, anti-HLA antibodies were detected in 10·6% of female and 4·3% of male donors without history of immunization. Of the antibody specificities found, 6 of 17 (35·3%) anti-HLA-A, 4 of 8 (50·0%) anti-HLA-B and 4 of 6 (66·6%) anti-HLA class II antibodies have been detected in donors associated with TRALI cases in the literature. Platelet apheresis donors without history of immunization have anti-leucocyte antibodies that potentially can cause TRALI. In our opinion, this cohort should be included in screening strategies for TRALI prevention. As references and consensus cut-offs have not yet been established, it is premature to use microbead assays as standard for donor screening.

Exploring of Primate Models of Tick-Borne Flaviviruses Infection for Evaluation of Vaccines and Drugs Efficacy

Tick-borne encephalitis virus (TBEV) is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV) in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8–16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to TBEV than C. aethiops.

Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector

Measles virus (MV) vectors are promising candidates for designing new recombinant vaccines since the parental live vaccines have a well-known safety and efficacy record. Like all viral vectors, the MV vector efficacy in inducing a protecting immune answer could be affected by the pre-existing immunity among the human population. In order to determine the optimal immunization route and regimen, we mimicked a MV pre-immunity by passively administrating MV neutralizing antibodies (MV-nAb) prior intramuscular (i.m.) and/or intranasal (i.n.) immunization with recombinant MV expressing the SIV-gag antigen (rMV-SIVgag). Our results revealed that 500 mIU of MV-nAb allowed the induction of a humoral and cellular immune response against the vector and the transgene, while higher titers of the MV-nAb were significantly inhibitory. In a prime-boost regimen, in the presence of MV-nAb, the intranasal-intramuscular (i.n.-i.m.) or intramuscular-intramuscular (i.m.-i.m.) routes induced higher humoral immune responses against the vector and the transgene (SIV-gag). In naive animals, cellular immune response was significantly higher by i.m. immunization; however, MV pre-immunity did not seem to affect the cellular immune response after an i.n. immunization. In summary, we show that a pre-existing immunity of up to 500 mIU anti-MV neutralizing antibodies had little effect on the replication of rMV and did not inhibit the induction of significant humoral and cellular immune responses in immune-competent mice.