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Objectives The 4CMenB vaccine confers protection against serogroup B invasive meningococcal disease (MenB IMD). Licensed worldwide based on immunogenicity and safety data, we now have data on its effectiveness and impact. We have exhaustively reviewed all the evidence gathered in the real world since the vaccine was licensed. Results Data from 7 countries provide evidence of effectiveness and impact in different settings and age groups, including national/regional immunisation programmes, observational studies, and outbreak control. The administration of at least 2 doses of 4CMenB reduced IMD by 50–100% in individuals from 2 months to 20 years of age. Estimation of the effectiveness of the vaccine in fully vaccinated cohorts ranged from 59 to 100%. The real-world safety profile of 4CMenB corresponded with the data from the clinical trials undertaken prior to its licensing. Conclusion MenB IMD is a rare but potentially fatal disease, with unpredictable epidemiology. The data on the effectiveness and impact data of 4CMenB support its use in the prevention of IMD. The results underline the importance of directly protecting the groups most at risk: infants/young children and adolescents. Direct protection through systematic immunisation in infancy (with salvage in young children) and systematic immunisation in adolescents could constitute the preferred model for the control of MenB disease. A Video Abstract linked to this article is available on Figshare: https://doi.org/10.6084/m9.figshare .

espanolObjetivos 4CMenB es una vacuna que confiere proteccion frente a la enfermedad meningococica invasiva por el serogrupo B (EMI por MenB). Autorizada en todo el mundo a partir de los datos de inmunogenicidad y seguridad, disponemos ahora de datos de su efectividad e impacto. Hemos revisado de manera exhaustiva toda la evidencia recopilada en el mundo real desde su autorizacion. Resultados Los datos de 7 paises aportan evidencia de efectividad e impacto en diferentes entornos y grupos de edad, incluidos programas de inmunizacion nacionales/regionales, estudios observacionales y control de brotes. La administracion de al menos 2 dosis de 4CMenB redujo la enfermedad meningococica invasiva (EMI) por MenB en un 50-100% en personas de 2 meses a 20 anos. Las estimaciones de la efectividad vacunal en las cohortes completamente vacunadas oscilaron entre el 59 y el 100%. El perfil de seguridad de 4CMenB en el mundo real se correspondio con los datos de los ensayos clinicos previos a su autorizacion. Conclusion La EMI por MenB es una enfermedad poco frecuente pero potencialmente mortal, con una epidemiologia imprevisible. Los datos sobre efectividad e impacto de 4CMenB respaldan su uso para la prevencion de la EMI. Los resultados subrayan la importancia de la proteccion directa de los grupos con mayor riesgo: lactantes/ninos pequenos y adolescentes. La proteccion directa a traves de la inmunizacion sistematica en los lactantes (con rescate de los ninos pequenos) y la vacunacion sistematica en la adolescencia podrian constituir la modalidad preferida para el control de la enfermedad por MenB. En Figshare encontrara un resumen en video relacionado con este articulo: https://doi.org/10.6084/m9.figshare. EnglishObjectives The 4CMenB vaccine confers protection against serogroup B invasive meningococcal disease (MenB IMD). Licensed worldwide based on immunogenicity and safety data, we now have data on its effectiveness and impact. We have exhaustively reviewed all the evidence gathered in the real world since the vaccine was licensed. Result Data from 7 countries provide evidence of effectiveness and impact in different settings and age groups, including national/regional immunisation programmes, observational studies, and outbreak control. The administration of at least 2 doses of 4CMenB reduced IMD by 50-100% in individuals from 2 months to 20 years of age. Estimation of the effectiveness of the vaccine in fully vaccinated cohorts ranged from 59 to 100%. The real-world safety profile of 4CMenB corresponded with the data from the clinical trials undertaken prior to its licensing. Conclusion MenB IMD is a rare but potentially fatal disease, with unpredictable epidemiology. The data on the effectiveness and impact data of 4CMenB support its use in the prevention of IMD. The results underline the importance of directly protecting the groups most at risk: infants/young children and adolescents. Direct protection through systematic immunisation in infancy (with salvage in young children) and systematic immunisation in adolescents could constitute the preferred model for the control of MenB disease.

Serogroup B meningococci (MenB) remain a prominent cause of invasive meningococcal disease (IMD). The protein-based multicomponent 4CMenB and the bivalent MenB-FHbp are the only currently available vaccines against MenB-caused IMD. Efficacy studies are not possible, due to the low incidence of IMD. Therefore, the vaccines' immunogenicity has been evaluated against several target strains chosen to quantify complement-mediated killing induced by each vaccine component in the serum bactericidal antibody assay. However, due to the wide genetic diversity and different expression levels of vaccine antigens across MenB strains, vaccine performance may differ from one strain to another. Here, we review the methods used to predict MenB strain coverage for 4CMenB and MenB-FHbp. Phenotypic assays such as the meningococcal antigen typing system (MATS, 4CMenB-specific) and the flow cytometric meningococcal antigen surface expression assay (MEASURE; MenB-FHbp-specific) were developed. Genomic approaches are also available, such as genetic MATS (gMATS) and the Bexsero antigen sequence type (BAST) scheme, both 4CMenB-specific. All methods allow tentative predictions of coverage across MenB strains, including that afforded by each vaccine antigen, and are rapid and reproducible. Real-world data on vaccine effectiveness are needed to confirm predictions obtained by these methods.

The multicomponent meningococcal serogroup B vaccine, 4CMenB, has demonstrated effectiveness in preventing invasive MenB disease in infants and in controlling MenB outbreaks. The need for/timing of additional booster doses is not yet established. We reviewed eight studies that evaluated antibody persistence and booster following primary 4CMenB vaccination of infants, children, adolescents, and young adults. Putative seroprotective hSBA titers for ≥1 vaccine antigen were maintained by 76–100% of children 24–36 months after priming during infancy and in 84–100% after priming in the second year of life. hSBA levels were higher in vaccinees at 4 and 7.5 years following priming during adolescence than in vaccine-naïve individuals of a similar age. Antibodies persisted at higher levels to NHBA and NadA than to PorA or fHbp. Booster vaccination induced robust anamnestic responses, demonstrating effective priming by 4CMenB across age-groups. These data can inform decision-making to optimize vaccination strategies.

This phase IV, single blind study assessed the immunogenicity and safety of India-manufactured purified chick embryo cell rabies vaccine (PCECV), compared with a German-manufactured batch obtained by the same production process. A total of 340 participants enrolled at 2 study sites in India were randomized (1:1:1:1) in 4 groups to receive a 5-dose Essen regimen with either 1 of the 3 Indian batches (PCECV-I) or the German batch (PCECV-G), administered on Days (D) 0, 3, 7, 14 and 30. The lot-to-lot consistency of PCECV-I batches in terms of induced immune response at D14 was demonstrated. The immune response elicited by PCECV-I was shown to be non-inferior to that induced by PCECV-G, as the lower limit of the 95% confidence interval for the ratio (PCECV-I/PCECV-G) of rabies virus neutralising antibody (RVNA) geometric mean concentrations was higher than 0.5 at D14. At least 96% of participants developed adequate RVNA concentrations (≥ 0.5 IU/mL) by D14 and all achieved RVNA concentrations ≥ 0.5 IU/mL by D90. RVNA levels were comparable across all groups throughout the entire study. Solicited local and general symptoms had a similar incidence in all groups. Unsolicited adverse events (AEs) were reported by 11% of participants. Only 1 serious AE (leg fracture) was reported and was not related to vaccination. No deaths and no rabies cases were recorded during the 90 days of observation. The study showed that the 3 PCECV-I and the PCECV-G batches induced a similar immune response and had a comparable safety profile when administered according to a 5-dose schedule.

Meningococcal disease is rare, easily misdiagnosed, and potentially deadly. Diagnosis in the early stages is difficult and the disease often progresses extremely rapidly. In North America, the incidence of invasive meningococcal disease (IMD) is highest in infants and young children, with a secondary peak in adolescents, a population predominantly responsible for the carriage of disease. Neisseria meningitidis serogroup B (MenB) accounts for a large proportion of meningococcal disease in North America, with documented outbreaks in three universities in the United States (US) during 2008–2013. Vaccination is the most effective way to protect against this aggressive disease that has a narrow timeframe for diagnosis and treatment. 4CMenB is a multi-component vaccine against MenB which contains four antigenic components. We describe in detail the immunogenicity and safety profile of 4CMenB based on results from four clinical trials; the use of 4CMenB to control MenB outbreaks involving vaccination at two US colleges during outbreaks in 2013–2014; and the use of 4CMenB in a Canadian mass vaccination campaign to control the spread of MenB disease. We discuss the reasons why adolescents should be vaccinated against MenB, by examining both the peak in disease incidence and carriage. We consider whether herd protection may be attained for MenB, by discussing published models and comparing with meningitis C (MenC) vaccines. In conclusion, MenB vaccines are now available in the US for people aged 10–25 years, representing an important opportunity to reduce the incidence of IMD in the country across the whole population, and more locally to combat MenB outbreaks.

Having previously demonstrated the feasibility of administering A/H5N1 and seasonal influenza vaccine antigens in an MF59-adjuvanted tetravalent formulation, we now report on long-term antibody persistence and responses to a booster dose of a combined seasonal-pandemic, tetravalent influenza vaccine in adults. The primary objective was the evaluation of responses to a booster dose of tetravalent influenza vaccine containing seasonal (A/H1N1, A/H3N2, and B) and avian (A/H5N1, clade 2) influenza virus strains administered to 265 healthy 18- to 40-year-old volunteers 1 year after priming with one or two clade 1 A/H5N1 doses. Secondary objectives were assessment of reactogenicity, safety, and antibody persistence 1 year after priming with a combined seasonal-pandemic, tetravalent vaccine. Responses to seasonal strains met all European licensure criteria; seroprotection rates were 94 to 100%, 100%, and 61 to 90% for A/H1N1, A/H3N2, and B strains, respectively. Anamnestic responses were observed against homologous and heterologous A/H5N1 strains whether priming with one or two A/H5N1 doses, with a monovalent A/H5N1 vaccine, or with a tetravalent vaccine. A single dose of MF59-adjuvanted A/H5N1 vaccine given alone or as part of a fixed combination with a seasonal influenza vaccine was sufficient to prime adult subjects, resulting in robust antigen-specific and cross-reactive antibody responses to heterologous booster immunization 1 year later. These data support the feasibility of incorporating prepandemic priming into seasonal influenza vaccination programs. (This study has been registered at clinicaltrials.gov under registration no. NCT00481065.)

Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59(®), an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence. Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad(®), a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population.

Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross- reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non-adjuvanted pre-pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre-pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross- reactive immunogenicity. MF59 � , the first oil-in-water emulsion

A total of 222 adult subjects, all of whom received primary immunization according to the rapid immunization schedule in a preceding clinical trial with either a new (i.e. polygeline free) or formerly licensed (i.e. polygeline containing) TBE vaccine were invited for extension studies. The subjects received the first booster immunization with the new TBE vaccine at 12 to 18 months after primary immunization. Subsequently, a total of 191 of the 222 subjects could be enrolled in a serological follow-up one year after the booster immunization. Neutralizing TBE antibody titers were determined prior to, 21 days after and approximately 12 months after booster immunization. Prior to first booster immunization, TBE antibodies (GMTs) had remained on a high level and were far above the detection limit of the neutralization test used. All subjects of the per protocol population who were primarily immunized with the new TBE vaccine formulation and all but one subject of the control group were still seropositive prior to the booster. All subjects showed a sharp increase of TBE antibodies following the booster immunization. Within the 12 months follow-up period, neutralizing TBE antibody titers remained on a high level. The booster vaccination was well tolerated by the subjects. Only very few febrile reactions (< 1%) none higher than 38.5 degrees C were reported. No serious or unexpected adverse events related to vaccination were reported. These successful results in terms of both immunogenicity and safety indicate that TBE vaccination with this new TBE vaccine can be used safely in adults. A long lasting immunity can be concluded from the strong immune response following the booster immunization.

Immunogenicity and safety of a booster dose of an MF59-adjuvanted H5N1 vaccine containing 7.5 μg A/turkey/Turkey/1/2005-like (clade 2.2) H5N1 hemagglutinin, given approximately 18 months after primary vaccination with a heterologous strain, were evaluated. The booster vaccine was well tolerated and induced a robust, cross-reactive immune response.

Primary immunization with two doses of MF59 (®) -adjuvanted A/H5N1 influenza vaccine has been shown to be highly immunogenic and well tolerated in children and adolescents. Assessment of long-term antibody persistence after priming, and the effects of a one-year booster dose in children and adolescents was needed.This study assessed homologous and heterologous antibody responses to a one-year booster dose of MF59-adjuvanted A/H5N1 influenza vaccine in previously primed children.Twelve months after primary vaccination, persistent, homologous, seroprotective HI antibody titers (≥ 40) were observed in 46%, 26% and 30% of toddlers, children and adolescents; following booster vaccination, seroprotection rates increased to 99%, 98% and 91%, respectively. All toddlers and children, and 99% of adolescents achieved MN antibody titers ≥ 40. Cross-reactive A/H5N1 antibodies were detected in 94-98% of subjects after booster vaccination.Twelve months after primary vaccination, toddlers, children and adolescents received a single booster dose of the same A/H5N1 vaccine. Paired sera were collected before and three weeks after booster vaccination. Homologous antibody responses against the A/Vietnam/1194/2004 vaccine strain were measured by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN) assays. Heterologous antibody responses against A/Indonesia/5/2005 and A/Anhui/1/2005 strains were assessed by MN assay only.Two priming doses of MF59-adjuvanted A/H5N1 vaccine resulted in homologous and heterologous antibody responses which persisted for up to one year after immunization. A one-year booster dose was highly immunogenic, generating high homologous and cross-reactive A/H5N1 antibody titers.

Proactive priming before the next pandemic could induce immune memory responses to novel influenza antigens. In an open-label study, we analyzed B cell memory and antibody responses of 54 adults who received 2 7.5-μg doses of MF59-adjuvanted A/Vietnam/1194/2004 clade 1 (H5N1) vaccine. Twenty-four subjects had been previously primed with MF59-adjuvanted or plain clade 0-like A/duck/Singapore/1997 (H5N3) vaccine during 1999–2001. The prevaccination frequency of circulating memory B cells reactive to A/Vietnam/1194/2004 was low in both primed and unprimed individuals. However, at day 21 after boosting, MF59-adjuvanted primed subjects displayed a higher frequency of H5N1-specific memory B cells than plain-primed or unprimed subjects. The immune memory was rapidly mobilized by a single vaccine administration and resulted in high titers of neutralizing antibodies to antigenically diverse clade 0, 1, and 2 H5N1 viruses already at day 7. In general, postvaccination antibody titers were significantly higher in primed subjects than in unprimed subjects. Subjects primed with MF59-adjuvanted vaccine responded significantly better than those primed with plain vaccine, most notably in early induction and duration of cross-reacting antibody responses. After 6 months, high titers of cross-reactive antibody remained detectable among MF59-primed subjects. We conclude that distant priming with clade 0-like H5N3 induces a pool of cross-reactive memory B cells that can be boosted rapidly years afterward by a mismatched MF59-adjuvanted vaccine to generate high titers of cross-reactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.

Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4+T cells broadly reactive with drifted H5. The CD4+response was dominated by IL-2+IFN-γ−IL-13−T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4+T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4+T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.

Background Pathogenic avian influenza virus (H5N1) has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed. Methods and Findings Healthy adults aged 18–60 and >60 years (n = 313 and n = 173, respectively) were randomized (1∶1) to receive two primary and one booster injection of 7.5 μg or 15 μg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) (clade 1) vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization assays (MN). Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 μg and 15 μg doses were comparable. The rates for seroprotection (HI>40; SRH>25mm2; MN ≥40) after the primary vaccination ranged 72–87%. Six months after primary vaccination with the 7.5 μg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 μg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations. Conclusions Both formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs. Trial Registration ClinicalTrials.gov NCT00311480

Tick-borne encephalitis (TBE) is an important, vaccine-preventable arthropod-borne disease, causing severe illness in children too. In order to evaluate the immune response to different licensed primary immunization schedules, a total of 294 children aged 1 to 11 years of age were enrolled in a randomized, controlled, multi-center trial. The subjects were vaccinated with the pediatric formulation of a TBE vaccine (Encepur children) according to the conventional schedule (Group C; N = 73, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M; N = 139, vaccination on days 0, 21 and 300), or the rapid schedule (Group R; N = 82, vaccination on Days 0, 7 and 21). Antibody titers as measured by neutralization-test (NT) and ELISA were determined on Days 0, 42, 180, 300, and 321. The demographic data of the study groups were similar. Most subjects (97%-100%) reached an NT titer of at least 1:10 on Day 42. On Day 42, the highest NT geometric mean titers (GMTs) were reached in Group C. In Group C and Group M, titers declined up to Day 300. Until Day 300, the highest NT-GMTs were maintained in Group R, notably without a decline compared to Day 42. Group M reached titers similar to Group R on Day 42, but these titers declined by 50% up to Day 180. Similar to the NT, on Day 42 highest geometric mean concentrations (GMCs) as measured by ELISA across all groups were reached in Group C. In all groups, titers declined until Day 300. On Day 300, GMC ELISA of Group R was higher compared to Group C and Group M. To conclude, the rapid immunization schedule in children not only provides fast protection but also leads to stable titers as measured by NT for at least 300 days after vaccination.

ecent cases of human rabies imported to Eu-rope by travelers visiting India and Morocco demonstrate the relevance and value of receiving proper education regarding rabies prevention, in-cluding both preexposure vaccination and postex-posure prophylaxis, prior to leaving for canine rabies – endemic countries. 1,2 This is especially rele-vant for travelers planning on visiting countries in Asia and Africa where the majority of human rabies cases occur. 3 Modern cell culture vaccines recommended by the World Health Organization (WHO), including purifi ed chick embryo cell vac-cine (PCECV), purifi ed Vero cell rabies vaccine, and human diploid cell rabies vaccine (HDCV), provide a safe means by which travelers can be pro-tected in the event of exposure to rabies virus. These vaccines have been licensed for several decades, but there are limited published data regarding the length of time after a person has received his or her primary rabies vaccination, for which they will continue to develop an anamnestic response after a booster dose of rabies vaccine has been adminis-tered. 4,5 The vaccination recommendations for a person who has been vaccinated previously with a cell culture rabies vaccine and is subsequently exposed to a rabid animal include the administra-tion of two booster doses of vaccine (one dose on day 0 and the other on day 3) without the adminis-tration of rabies immunoglobulin (RIG). However, the limited amount of available data has led to some confusion regarding booster recommendations in previously vaccinated persons who are subse-quently exposed to rabid animals. 6,7 To determine how long individuals would be able to mount an anamnestic response after primary vac-cination, we contacted all veterinarians who had ini-tially received PCECV as students enrolled in a clinical trial initiated in 1986. 8 The veterinarians who agreed to participate in this booster study veri-fi ed and confi rmed that they had not received a rabies booster vaccination for 14 years since the clin-ical trial was completed, and all agreed to provide their serum samples for serological evaluation before and after receiving a booster dose of rabies vaccine. In the initial clinical trial conducted in 1986, 78 individuals were vaccinated with either HDCV or PCECV intramuscularly or intradermally as a pri-mary three-dose series. 8 In 1988, 68 of the 78 subjects received a single 1.0 mL of PCECV in tramuscularly. After the booster dose in 1988, the mean titer for subjects who received intradermal dosage initially was 1,106 (range: 270 – 6,800) and for subjects who received intramuscular dosage for their initial series was 1,859 (range: 1,100 – 9,500). For comparison purposes, a reciprocal titer of 1:25 is approximately equal to a titer of 0.5 IU/mL. Fourteen years later, 15 of those who initially received PCECV and a dose of intramuscular booster 1 year after their primary se-ries and who had not received any additional rabies vaccination since the 1988 booster were enrolled in this study. After approval of the study by the ethics committee and obtaining informed consent from the subjects, a blood sample was obtained and a single

Haemophilus influenzae type b (Hib) infection remains a major public health problem in the developing world. We evaluated the safety and immunogenicity of a new PRP-CRM197 conjugate Hib vaccine (Vaxem Hib, Chiron Vaccines), compared with the HibTITER vaccine (Wyeth-Lederle Vaccines), following the World Health Organisation (WHO)'s accelerated schedule which allows 4-week intervals between doses.A phase II, observer-blind, multicentre, randomised, controlled, non-inferiority study.In total, 331 babies were immunised with either Vaxem Hib (N = 167) or HibTITER (N = 164) vaccine at 6, 10 and 14 weeks of age, in parallel with oral polio, diphtheriatetanus-pertussis and hepatitis B vaccines. Post-immunisation reactions were recorded after each immunisation and at follow-up visits. Anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assays (ELISAs) before and 1 month after the third immunisation.Overall, there was no significant difference in the anti-PRP levels between the two groups. One month after the third immunisation, 76% of vaccinees in the Vaxem Hib group and 70% in the HibTITER group had anti-PRP antibody titresor = 1.0 microgram/ml, while 96% of the Vaxem Hib group and 90% of the HibTITER group demonstrated anti-PRP antibody titresor = 0.15 microgram/ml. The geometric mean titre at day 90 was 3.77 micrograms/ml for the Vaxem Hib and 3.0 micrograms/ml for the HibTITER groups. Although the Vaxem Hib vaccine produced more redness (6% versus 1%; p = 0.006) and swelling (5% versus 1%, p = 0.037), overall it was well tolerated compared with the HibTITER vaccine. There was no significant difference in vaccine-related elevated temperature (or = 38 degrees C) between the two groups (p = 0.11).Both vaccines showed comparable safety and immunogenicity profiles when administered to South African babies at 6, 10 and 14 weeks of age.

Background: Since 2006 when the zoster vaccine was first icensed, one of the most commonly asked questions by patients nd clinicians has been “Should a patient with a history of herpes oster (HZ) receive the vaccine to prevent another episode?”. The enefit of vaccinating immunocompetent patients who have had hingles has not been examined. The study assessed the association etween vaccination and the incidence of herpes zoster recurrence mong personswith a recent episode of clinically diagnosed herpes oster. Methods: This is a matched cohort study in Kaiser Permanente outhern California. Study populations were immunocompetent lderly≥ 60 years oldwith a recent episode of herpes zoster. Potenial recurrent HZ cases were identified electronically by ICD-9 code f 053.xx from outpatient, emergency, and inpatient files. Medcal records of electronically identified cases were retrieved and eviewed masked to vaccination status by an infectious disease pecialist using pre-specified review criteria. Incidence of recurent herpes zoster was compared between the vaccinated and the nvaccinated matched cohorts. The hazard ratio associated with accination was adjusted for a propensity score that accounted for otential confounders. Results: There were total 1,036 vaccinated and 5,180 unvacciated members included. Based on the clinically confirmed cases, he incidence of recurrent HZ among age

As part of an epidemiological study that aims to characterize chemically the mutation(s) in transthyretin (TTR) related to familial amyloidotic polyneuropathy (FAP) of different ethnic origins, studies were carried out on TTR from two FAP kindreds of Italian origin. Two different criteria were employed in the characterization of TTR from these kindreds: (1) immunoblotting of cyanogen bromide fragments for screening of TTR(Met30) and (2) isoelectric focusing. TTR(Met30) was not detected but other substitutions were demonstrated using isoelectric focusing techniques. One of the variants found is a basic TTR variant. The substitutions occurring in the variant TTRs of these two kindreds are not known and are presently under study.