Effectiveness of a commercial leptospiral vaccine on urinary shedding in naturally exposed sheep in New Zealand

L. borgpetersenii serovar Hardjo and L. interrogans serovar Pomona are endemic in New Zealand sheep. An effective vaccine and vaccination strategy would protect both humans and livestock.Four to 12 lambs were selected from each of eight farms (total = 84, vaccinated group), while four to 16 lambs (total = 98) served as unvaccinated controls. A commercial Hardjo/Pomona vaccine was given at 1–6 weeks of age, 5–11 weeks later and 33–67 weeks later on seven farms and at 18 weeks of age and 5 weeks later on the eighth farm. Vaccinates and controls were grazed together. Blood was regularly collected from the control group to assess flock exposure. Urine was collected from both groups 26–82 weeks after the second vaccination and tested by quantitative PCR.Seroprevalence in controls at the time of urine sampling ranged from 2.7 to 98.2% for Hardjo and from 0 to 54.1% for Pomona with seroconversion occurring 13 to 67 weeks after the second vaccination in all but one farm where exposure had happened by the time of vaccination. The shedding prevalence adjusted for clustering in farms was 45.1% [95% CI 17.6–72.7] (for an observed number of 50/98) in the control animals and 1.8% [95% CI 0.0–10.1] (for an observed number of 5/84) in the vaccinated animals. The vaccine was 100% effective on five farms where animals were vaccinated before 12 weeks of age and before natural exposure occurred, but the effectiveness was 80% [0–97] on one farm where the lambs were exposed before vaccination and 65% [9–87] to 80% [0–97] on one farm where the animals were fully vaccinated by 24 weeks of age. The overall vaccine effectiveness was 86.3% [63.6–94.8%] despite maternal antibodies in some flocks at first vaccination. Vaccination timing seemed to be crucial in achieving optimum reduction in shedding in urine in vaccinated sheep.     

Immunogenicity and protective efficacy of virus-like particles and recombinant fiber proteins in broiler-breeder vaccination against fowl adenovirus (FAdV)-8b

Inclusion body hepatitis (IBH) is an economically important diseases in broiler chicken industry. Several serotypes of fowl adenovirus (FAdV) can cause IBH, among them, serotype FAdV-8b is associated with the majority of the IBH cases in Canada. Here, we evaluated FAdV-8b virus-like particles (VLPs) and recombinant FAdV-8b fiber proteins (expressed in E. coli) as potential broiler-breeder vaccines against IBH. For assessing the immunogenicity of vaccines, we investigated both humoral and cellular immunity. The humoral immune response was evaluated by determining total IgY and virus-neutralizing antibody in serum at 14, 28, 35 and 60 days post-immunization (dpi). We examined cellular immunity using flow cytometry by determining CD4:CD8 ratio change in peripheral blood after the booster vaccination. The protective effect of vaccines was tested by challenging 14 day-old progeny (n = 30/group) carrying maternal antibodies (MtAb) by challenging with virulent FAdV-8b virus (1 × 10⁷ TCID₅₀, FAdV-8b-SK). Although total IgY levels were comparable in all groups, the neutralizing antibody response in broiler-breeders at 35 and 60 dpi was significantly (p < 0.05) higher those vaccinated with FAdV-8b VLPs followed by FAdV-8b fiber compared to fiber-knob. Moreover, vaccines comprised of FAdV-8b VLPs and FAdV-8b fiber rather than FAdV-8b fiber-knob efficiently elicited the cell-mediated immune response as evidenced by a statistically significant (p < 0.05) CD8⁺ T-cell proliferative response in broiler-breeders four days after the booster vaccination. Unlike FAdV-8b fiber-knob, FAdV-8b VLPs, and FAdV-8b fiber vaccinated broiler-breeders were able to transfer a substantial amount (28.4 ± 9%) of MtAb to their progeny. Challenge revealed that MtAb provided 100% and 82.7% protection in progeny hatched from FAdV-8b VLPs, and FAdV-8b fiber vaccinated broiler-breeders, respectively. Collectively, our data suggest that FAdV-8b subunit vaccine-induced MtAb efficiently protected progeny against clinical IBH and broiler-breeder vaccination with subunit vaccines is a potential approach to protect against IBH.     

Rubella specific cell-mediated and humoral immunity following vaccination in college students with low antibody titers

ObjectiveThis study measured cell-mediated immunity (CMI) and antibodies to clarify the basis of rubella reinfection after vaccination.MethodsIn a pool of 65 college students, 39 who exhibited hemagglutination–inhibition (HI) antibody titers against rubella of ≤1:16 were vaccinated with a rubella vaccine. The CMI was assessed with interferon-gamma release assay.ResultsThere was low correlation (r = 0.24) between the antibody titers and interferon-gamma levels at pre-vaccination status. Preexisting interferon-gamma levels were low in some subjects with low HI antibody titers of 1:8 and 1:16. Fifty-seven percent (4/7) of the subjects who were antibody-negative with past history of rubella vaccination at entry onto the study exhibited CMI. And 57% (4/7) of the subjects remained antibody-negative following a second vaccination, despite exhibiting CMI. HI antibody titers increased significantly after vaccination, whereas post-vaccination interferon-gamma levels did not exhibit significant increases. When subjects were divided (based on their past history of vaccination and antibody values) into natural infection and vaccination groups, HI antibody titers (mean ± SD) increased to 1:2^4.4 ± 1.4 from 1: 2^3.2 ± 0.4 (p = 0.065) in the natural infection group and to 1:2^4.4 ± 1.0 from 1:2^3.0 ± 0.8 (p < 0.00001) in the vaccination group following vaccination. The same classification revealed that interferon-gamma values did not increase significantly in either group following vaccination, but the interferon-gamma values at pre- and post-vaccination in the natural infection group were significantly higher than those at pre- and post-vaccination in the vaccination group (p < 0.05 and p < 0.05, respectively).ConclusionPre-vaccination interferon-gamma levels in each HI antibody titer group were similar. And there were some subjects with antibody-positive exhibited CMI-negative. These data may explain why rubella reinfection can occur in vaccinated seropositive individuals.     

Rotavirus vaccination compliance and completion in a Medicaid infant population

We examined completion and compliance rates of rotavirus (RV) vaccination according to the recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Food and Drug Administration approved Prescribing Information (PI) for Rotarix^® (RV1, GlaxoSmithKline Vaccines) and RotaTeq^® (RV5, Merck and Co.) among infants under one year of age covered by Medicaid programs. Healthcare claims data from state Medicaid programs that constituted the Truven Health MarketScan^® Multi-State Medicaid Database were retrieved from May 2008–June 2012. Infants were grouped under PI and ACIP cohorts based on the dosing regimens followed. The overall compliance per PI (n = 673,956) and ACIP (n = 695,612) recommendations were 24.5% and 28.2%, respectively; completion rates were 30.3% and 32.6%, respectively. In the PI cohort, infants who received RV1 had significantly higher compliance as compared with infants who received RV5 (65.2% vs. 31.3%; p < 0.0001); completion rates among infants receiving RV1 and RV5 were 65.3% and 46.4%, respectively (p < 0.0001). In the ACIP cohort, compliance with RV1 was significantly higher than RV5 (68.8% vs. 45.9%; p < 0.0001) as was the overall completion rate (73.5% vs. 48.8%; p < 0.0001). While compliance is increasing year over year, overall compliance of RV vaccines is suboptimal, with over 40% of eligible infants unvaccinated in both populations. The 2-dose RV vaccine showed better completion rates and higher compliance than the 3-dose RV vaccine in the United States. Public health initiatives focusing on suboptimal compliance and completion rates of RV vaccination in the Medicaid population could improve these metrics, thereby offering protection against RV infection.     

Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumatoid arthritis: A prospective,open-label,multi-centre study

BackgroundTick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX).MethodsTBE vaccine, FSME-Immune^® or Encepur^®, was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test.ResultsThe study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n = 16), TNFi + MTX (n = 36) or MTX (n = 14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p = <0.05).ConclusionsStandard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.     

First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

BackgroundH56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tuberculosis (M.tb) infection.MethodsLow dose (15 μg H56 protein in 500 nmol IC31) or high dose (50 μg H56, 500 nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA.ResultsOne hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4⁺ T cells. M.tb-infected vaccinees had higher frequencies of H56-induced CD4⁺ T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ⁺TNF-α⁺IL-2⁺) and higher frequencies of H56-specific CD4⁺ T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4⁺ T cells, displaying a CD45RA⁻CCR7⁻ effector memory phenotype, emerged after the second high-dose vaccination in M.tb-infected vaccinees. TNF-α⁺IL-2⁺ H56-specific memory CD4⁺ T cells were detected mostly after low-dose H56 vaccination in M.tb-infected vaccinees, and predominantly expressed a CD45RA⁻CCR7⁺ central memory phenotype. Our results support further clinical testing of H56:IC31.     

Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge

The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0 × 10⁸ to 2.1 × 10¹¹ particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R² = 0.97) and viremia (R² = 0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R² = 0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge.     

Assessment of safety and reproductive performance after vaccination with a modified live-virus PRRS genotype 1 vaccine in pregnant sows at various stages of gestation

The objective of the present study was to assess safety and efficacy of a new modified live-virus porcine reproductive and respiratory syndrome (PRRS) genotype 1 vaccine in pregnant sows at various stages of gestation under field conditions. A total of 505 sows and gilts were allocated to two treatment groups and maintained in separate facilities. Animals of group 1 were vaccinated with a commercial modified live genotype 1 PRRSV vaccine (control product, CP), while animals of group 2 were immunized with a new modified live genotype 1 PRRSV vaccine (investigational veterinary product, IVP) (ReproCyc® PRRS EU, Boehringer Ingelheim Vetmedica GmbH). Injection site reactions were noted to be significantly less frequent in the IVP group compared to the CP group for pain (p = 0.039), redness (p = 0.030), heat (p = 0.016) and swelling (p = 0.002). The mean total number of piglets alive at weaning did not differ significantly between both study groups (10.6 vs. 11.0, p = 0.375). However, pre-weaning mortality was significantly higher (p = 0.005) in piglets from the CP group (14.1% vs. 10.9%). Analyses of reproductive performance data for both groups did not result in statistically significant differences between CP group and IVP group for number of piglets alive (12.7 and 12.6, respectively), healthy live (11.9 and 11.8), weak (0.7 and 0.5), stillborn (1.0 and 0.8) and mummified piglets (0.3 and 0.2) per litter. No differences were detected between both groups for piglet birth weights, while body weights at weaning (7.2 kg vs. 6.6 kg, p = 0.026) and average daily gain (0.2445 kg vs. 0.2211 kg, p = 0.037) were significantly higher in piglets from the IVP group. In conclusion, the administration of a single dose of ReproCyc® PRRS EU to sows and gilts at various stages of gestation confirmed non-inferiority to a commercial PRRS vaccine regarding safety and efficacy parameters under field conditions.     

Vaccination of koalas with a prototype chlamydial vaccine is safe,does not increase the incidence of lymphoma-related disease and maybe associated with increased lifespan in captive koalas

ObjectivesTo assess the impact of Chlamydia vaccination on survival of captive koalas, and to compare the incidence of lymphomas and neoplasias between vaccinated and unvaccinated koalas.MethodsSurvival analysis using Cox and Weibull regressions on 54 vaccinated and 52 matched unvaccinated koalas, and chi-square contingency table for incidence of lymphomas/neoplasias.ResultsVaccination was found to have a significant positive effect on koala lifespan (P = 0.03), with vaccinated koalas having a median lifespan of 12.25 years compared to 8.8 years for unvaccinated ones. The effect of sex on lifespan was not significant (P = 0.31). The risk ratio of unvaccinated over vaccinated koalas was 2.2 with both Cox and Weibull regressions. There was no association between the incidence of lymphoma/neoplasias and vaccination status (P = 0.33).ConclusionsKoalas vaccinated with a prototype Chlamydia vaccine may live longer than unvaccinated ones. There was no known Chlamydia infection among koalas, so our interpretation is that vaccination may have boosted the innate and adaptive immune systems to protect against a wide spectrum of bacteria, fungi and parasites. Vaccinated koalas did not show negative physiological effects of the vaccine, for example, the frequency of deaths due to lymphomas/neoplasias was the same in both vaccinated and unvaccinated animals.     

Modified live infectious bursal disease virus (IBDV) vaccine delays infection of neonatal broiler chickens with variant IBDV compared to turkey herpesvirus (HVT)-IBDV vectored vaccine

Chickens are commonly processed around 35–45 days of age in broiler chicken industry hence; diseases that occur at a young age are of paramount economic importance. Early age infection with infectious bursal disease virus (IBDV) results in long-lasting immunosuppression and profound economic losses. To our knowledge, this is the first study comparing the protection efficacy of modified live (MdLV) IBDV and herpesvirus turkey (HVT)-IBDV vaccines against early age variant IBDV (varIBDV) infection in chicks. Experiments were carried out in IBDV maternal antibody (MtAb) positive chicks (n = 330), divided into 6 groups (n = 50–60/group), namely Group 1 (saline), Group 2 (saline + varIBDV), Group 3 (HVT-IBDV), Group 4 (HVT-IBDV + varIBDV), Group 5 (MdLV) and Group 6 (MdLV + varIBDV). HVT-IBDV vaccination was given via the in ovo route to 18-day-old embryonated eggs. MdLV was administered via the subcutaneous route in day-old broilers. Group 2, Group 4 and Group 6 were orally challenged with varIBDV (SK-09, 3 × 10³ EID₅₀) at day 6 post-hatch. IBDV seroconversion, bursal weight to body weight ratio (BBW) and bursal histopathology were assessed at 19 and 35 days of age. Histopathological examination at day 19 revealed that varIBDV-SK09 challenge caused severe bursal atrophy and lower BBW in HVT-IBDV but not in MdLV vaccinated chicks. However by day 35, all challenged groups showed bursal atrophy and seroconversion. Interestingly, RT-qPCR analysis after varIBDV-SK09 challenge demonstrated an early (9 days of age) and significantly high viral load (∼5744 folds) in HVT-IBDV vaccinated group vs unvaccinated challenged group (∼2.25 folds). Furthermore, flow cytometry analysis revealed inhibition of cytotoxic CD8⁺ T-cell response (CD44-downregulation) and decreased splenic lymphocytes counts in chicks after HVT-IBDV vaccination. Overall, our data suggest that MdLV delays varIBDV pathogenesis, whereas, HVT-IBDV vaccine is potentially immunosuppressive, which may increase the risk of early age varIBDV infection in broilers.     

Anti-tumor effect of the alphavirus-based virus-like particle vector expressing prostate-specific antigen in a HLA–DR transgenic mouse model of prostate cancer

The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F₁ male mice expressing human PSA and HLA-DRB1^*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV–PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP–PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV–PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA_65–73. In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2D^b/PSA_65–73 dextramers. VLPV–PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV–PSA vaccinated mice was significantly delayed at early time points (p = 0.002, Gehan–Breslow test). Our data suggest that TC-83-based VLPV–PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV–PSA vaccine will undergo further testing for the immunotherapy of prostate cancer.     

A commercial PCV2a-based vaccine significantly reduces PCV2b transmission in experimental conditions

Transmission characteristics of PCV2 have been compared between vaccinated and non-vaccinated pigs in experimental conditions. Twenty-four Specific Pathogen Free (SPF) piglets, vaccinated against PCV2 at 3 weeks of age (PCV2a recombinant CAP protein-based vaccine), were inoculated at 15 days post-vaccination with a PCV2b inoculum (6 ⋅ 10⁵ TCID₅₀), and put in contact with 24 vaccinated SPF piglets during 42 days post-inoculation. Those piglets were shared in six replicates of a contact trial involving 4 inoculated piglets mingled with 4 susceptible SPF piglets. Two replicates of a similar contact trial were made with non-vaccinated pigs. Non vaccinated animals received a placebo at vaccination time and were inoculated the same way and at the same time as the vaccinated group. All the animals were monitored twice weekly using quantitative real-time PCR and ELISA for serology until 42 days post-inoculation. The frequency of infection and the PCV2 genome load in sera of the vaccinated pigs were significantly reduced compared to the non-vaccinated animals. The duration of infectiousness was significantly different between vaccinated and non-vaccinated groups (16.6 days [14.7;18.4] and 26.6 days [22.9;30.4] respectively). The transmission rate was also considerably decreased in vaccinated pigs (β = 0.09 [0.05–0.14] compared to β = 0.19 [0.11–0.32] in non-vaccinated pigs). This led to an estimated reproduction ratio of 1.5 [95% CI 0.8 – 2.2] in vaccinated animals versus 5.1 [95% CI 2.5 – 8.2] in non-vaccinated pigs when merging data of this experiment with previous trials carried out in same conditions.     

Expression of fibronectin binding protein A (FnBPA) from Staphylococcus aureus at the cell surface of Lactococcus lactis improves its immunomodulatory properties when used as protein delivery vector

A recombinant strain of Lactococcus lactis displaying a cell-surface anchored fibronectin binding protein A (FnBPA) from Staphylococcus aureus (LL-FnBPA) had been shown to be more efficient in delivering plasmid than its wild-type counterpart both in vitro and in vivo, and have the ability to orientate the immune response toward a Th2 profile in a context of a DNA vaccination. The aim of this work was to test whether this LL-FnBPA strain could shape the immune response after mucosal administration in mice. For this, we used a mouse model of human papilloma virus (HPV)-induced cancer and a L. lactis strain displaying at its cell surface both HPV-16-E7 antigen (LL-E7) and FnBPA (LL-E7 + FnBPA). Our results revealed a more efficient systemic Th1 immune response with recombinant LL-E7 + FnBPA. Furthermore, mice vaccinated with LL-E7 + FnBPA were better protected when challenged with HPV-16-induced tumors. Altogether, the results suggest that FnBPA displays adjuvant properties when used in the context of mucosal delivery using L. lactis as a live vector.     

Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge

ObjectivesTo test vaccines, formulated with novel antigens, to protect mice against Chlamydia infections.MethodsTo determine the ability of polymorphic membrane proteins (Pmps) to induce cross-species protective immune responses, recombinant fragments from all nine C. trachomatis serovar E Pmps were used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 as adjuvants. C. muridarum recombinant MOMP and PBS, formulated with the same adjuvants, were used as positive and negative controls, respectively. Mice were challenged intranasally with 10⁴ inclusion-forming units (IFU) of C. muridarum. Animals were weighed daily and at 10 days post-challenge, they were euthanized, their lungs harvested, weighed and the number of chlamydial IFU counted.ResultsFollowing vaccination the nine Pmps elicited immune responses. Based on body weight changes, or number of IFU recovered from lungs, mice vaccinated with Pmp C, G or H were the best protected. For example, over the 10-day period, the negative control group vaccinated with PBS lost significantly more body weight than mice immunized with PmpC or G (P < 0.05). C. muridarum MOMP vaccinated mice were better protected against body weight losses than any group immunized with Pmps. Also, the median number of IFU recovered from the lungs of mice vaccinated with PmpC (72 × 10⁶) or PmpH (61 × 10⁶) was significantly less than from mice immunized with PBS (620 × 10⁶; P < 0.05). As determined by the number of IFU, all Pmps elicited less protection than C. muridarum MOMP (0.078 × 10⁶ IFU; P < 0.05).ConclusionsThis is the first time PmpC has been shown to elicit cross-species protection against a respiratory challenge. Additional work with Pmps C, G and H is recommended to determine their ability to protect animal models against genital and ocular challenges.     

Knowledge,attitude and awareness among healthcare professionals about influenza vaccination in Peshawar,Pakistan

A cross-sectional study was carried out among HCPs in Northwest General Hospital & Research Centre, Hayatabad Peshawar, Pakistan. The purpose of this study was to investigate knowledge, awareness and attitude of HCPs towards influenza vaccination. A total of N = 170 questionnaires were distributed among the staff. There was a 97% response rate to this survey (n = 165). The median age of the respondents was 30 years and most of them, 98 (59.0%), were from age group of 24–30 years. The majority of the HCPs that participated in this study were male 106 (64.2%), and by profession, the majority were physicians 77 (46.7%), followed by pharmacists and nurses. A majority 114 (69.1%) believed that it was not compulsory for HCPs to get vaccinated for influenza. Top three identified barriers to vaccination were: not everyone is familiar with the availability of the influenza vaccination at their institution (Relative importance weight factors (RIWF) = 0.71), due to needle fear I do not like to get vaccinated (RIWF = 0.70) and it is not compulsory for healthcare professionals to get vaccinated for influenza (RIWF = 0.64). The logistic regression analysis has revealed association for job experience and profession with the most of the eleven knowledge item. However, when overall sum of eleven items were tested to identify the factors affecting the knowledge score, along with profession (−0.215 [−0.389 to 0.040]; p = 0.016) and job experience (0.823 [0.521–1.125]; p < 0.001) HCPs age (−0.409 [−0.755 to −0.064]; p = 0.020) was found to be another significant factor affecting the total knowledge score of HCPs. Overall, scoring of the correct responses revealed that nurses have better knowledge and understanding about influenza and the influenza vaccination (6.5 ± 0.8, p < 0.001*), followed by pharmacists (6.3 ± 1.14) and physicians. In spite of the published guidelines and recommendations, a very low percentage of the healthcare professionals in our hospital were vaccinated against influenza, and the barriers to vaccination were prevalent. Various strategies, including arranging seminars regarding awareness about vaccinations, are required to improve the knowledge and overall outcomes.     

Prime-booster vaccination of cattle with an influenza viral vector Brucella abortus vaccine induces a long-term protective immune response against Brucella abortus infection

This study analyzed the duration of the antigen-specific humoral and T-cell immune responses and protectiveness of a recently-developed influenza viral vector Brucella abortus (Flu-BA) vaccine expressing Brucella proteins Omp16 and L7/L12 and containing the adjuvant Montadine Gel01 in cattle. At 1 month post-booster vaccination (BV), both humoral (up to 3 months post-BV; GMT IgG ELISA titer 214 ± 55 to 857 ± 136, with a prevalence of IgG2a over IgG1 isotype antibodies) and T-cell immune responses were observed in vaccinated heifers (n = 35) compared to control animals (n = 35, injected with adjuvant/PBS only). A pronounced T-cell immune response was induced and maintained for 12 months post-BV, as indicated by the lymphocyte stimulation index (2.7 ± 0.4 to 10.1 ± 0.9 cpm) and production of IFN-γ (13.7 ± 1.7 to 40.0 ± 3.0 ng/ml) at 3, 6, 9, and 12 months post-BV. Prime-boost vaccination provided significant protection against B. abortus infection at 3, 6, 9 and 12 months (study duration) post-BV (7 heifers per time point; alpha = 0.03–0.01 vs. control group). Between 57.1 and 71.4% of vaccinated animals showed no signs of B. abortus infection (or Brucella isolation) at 3, 6, 9 and 12 months post-BV; the severity of infection, as indicated by the index of infection (P = 0.0003 to <0.0001) and rates of Brucella colonization (P = 0.03 to <0.0001), was significantly lower for vaccinated diseased animals than appropriate control animals. Good protection from B. abortus infection was also observed among pregnant vaccinated heifers (alpha = 0.03), as well as their fetuses and calves (alpha = 0.01), for 12 months post-BV. Additionally, 71.4% of vaccinated heifers calved successfully whereas all pregnant control animals aborted (alpha = 0.01). Prime-boost vaccination of cattle with Flu-BA induces an antigen-specific humoral and pronounced T cell immune response and most importantly provides good protectiveness, even in pregnant heifers, for at least 12 months post-BV.     

Meningococcal C conjugate age-dependant long-term loss of effectiveness

IntroductionAlthough different epidemiological studies have assessed meningococcal C conjugate vaccine effectiveness within 1 and >1 year since vaccination, none of them evaluated long-term effectiveness. In order to assess if epidemiological data correlates with the findings described in seroprevalence studies we evaluated long-term vaccine effectiveness over time, up to 10 years since vaccination.MethodsCases targeted by vaccination programs and notified to the Spanish Surveillance System between 2001 and 2013 were included in the study. Vaccine effectiveness was estimated using the screening method. Relationship between vaccine effectiveness and time since vaccination was explored using point estimates, simple logistic regression or restricted cubic splines logistic regression model for all and for those vaccinated at <1, 1–11 and at 12–19 years of age.ResultsFrom 345 confirmed cases reported in the period and targeted by vaccination programs, 125 (36.23%) were vaccine failures. Proportion of vaccine failures decreased with age of vaccination: 63.97% at <1 year; 36.84% at 1–11 years; and 3.88% at 12–19 years. Using the best model for each group, vaccine effectiveness decreased from 99.12% to 90.85% (%change = −8.3%) for all; from 99.04% to 48.60% (%change = −50.9%) for those vaccinated at <1 years and from 99.45% to 90.18% (%change = −9.3%) for those vaccinated at 1–11 years after 10 years since vaccination. For those vaccinated at 12–19 years no changes were observed in vaccine effectiveness after 10 years (p = 0.968).ConclusionsAfter 10 years, vaccine effectiveness decreased by 50% in those vaccinated at <1 year, while those vaccinated with one dose at 12–19 years showed no changes. Vaccine failures occurred early after vaccination and more frequently in those vaccinated at younger ages. Vaccination at ≥12 years seems to be related to a low number of vaccine failures and a higher and endurable protection over time.     

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers

An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines.In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix^® (GlaxoSmithKline), Typhim Vi^® (Sanofi Pasteur MSD) or Hepatyrix^® (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (−1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA.Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 μg/ml versus 6.13 μg/ml, P = 0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 μg/ml versus 14.58 μg/ml, P = 0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0.In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines.     

Immunogenicity of a low-dose diphtheria,tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria,tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap–IPV, Repevax^®; Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis^®; Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap–IPV, Tetravac^®; Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection.All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01 IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap–IPV, Tdap + OPV and DTap–IPV, respectively, had protective antitoxin levels greater than 0.1 IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV.Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.     

Vaccination status and immune response to 13-valent pneumococcal conjugate vaccine in asplenic individuals

Overwhelming post-splenectomy infection (OPSI) is immediately life-threatening and vaccination against encapsulated bacteria, in particular pneumococci, decreases its incidence.First, we investigated the adherence to vaccination guidelines in a retrospective study of the hospital records of splenectomised patients. Second, patients were asked to complete a questionnaire and invited to participate in a study where 12-valent pneumococcal serotype-specific IgG concentrations were determined before and 4 to 6 weeks after vaccination with PCV13.Of 79 individuals who underwent splenectomy between 2000 and 2012: 81.0% received pneumococcal vaccine, 51.9% received vaccine against Haemophilus influenzae type B and 22.8% received meningococcal vaccine. 31 individuals were deceased. 33 individuals completed questionnaires and accepted participation in the second part of the study. The participants consisted of two groups: (1) prior PPV23 (n = 24) and (2) prior PPV23 + PCV13 (n = 9). In group 1, pre-PCV13 GMC's ≥ 0.35 μg/mL were observed for serotypes 1, 4, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, and GMC's < 0.35 μg/mL for serotypes 3 and 5, significant increases pre- to post-PCV13 were found for serotypes 1, 3, 4, 5, 7F, 18C, 19A, 23F (p ≤ 0.001) and 19F (p = 0.01) and all 12 serotypes-specific GMC were above 0.35 μg/mL after vaccination. Group 2 did not receive vaccine in this study, but blood tests showed all 12 serotype-specific GMC > 0.35 μg/mL.Adherence to guidelines regarding primary pneumococcal vaccination was adequate but only a minority received the recommended meningococcal vaccination.High levels of pneumococcal serotype-specific antibodies were observed in the previous PPV23 vaccinated group, and more pronounced in the previous PCV13 group, and our data suggests that PCV13 is immunogenic for serotypes 1, 3, 4, 5, 7F, 18C, 19A, 19F and 23F, if used as a booster dose in asplenic patients with previous PPV23 vaccination.