Antibodies induced by vaccination with purified chick embryo cell culture vaccine (PCECV) cross-neutralize non-classical bat lyssavirus strains

Tissue-culture vaccines like purified chick embryo cell vaccine (PCECV) have been shown to provide protection against classical rabies virus (RABV) via pre-exposure or post-exposure prophylaxis. A cross-neutralization study was conducted using a panel of 100 human sera, to determine, to what extent after vaccination with PCECV protection exists against non-classical bat lyssavirus strains like European bat lyssavirus (EBLV) type 1 and 2 and Australian bat lyssavirus (ABLV). Virus neutralizing antibody (VNA) concentrations against the rabies virus variants CVS-11, ABLV, EBLV-1 and EBLV-2 were determined by using a modified rapid fluorescent focus inhibition test. For ABLV and EBLV-2, the comparison to CVS-11 revealed almost identical results (100% adequate VNA concentrations ≥0.5 IU/mL; correlation coefficient r² = 0.69 and 0.77, respectively), while for EBLV-1 more scattering was observed (97% adequate VNA concentrations; r² = 0.50). In conclusion, vaccination with PCECV produces adequate VNA concentrations against classical RABV as well as non-classical lyssavirus strains ABLV, EBLV-1, and EBLV-2.     

Feline herpesvirus vectored-rabies vaccine in cats: A dual protection

In China, cats cause about 5% of human rabies cases. Rabies control in cats plays a role in achieving the ultimate goal of elimination of dog rabies-mediated human deaths. However, there is no cat-specific rabies vaccine in China yet. In this study, we constructed a recombinant rabies vaccine by using a felid herpesvirus 1 (FHV-1) isolate, and deleted the gI/E in the FHV-1 and replaced the region with a glycoprotein (G) of rabies virus (RABV) strain BD06 through homologous recombination. The recombinant virus FHV-RVG was recovered and purified, and the expression of RABV glycoprotein was verified by indirect immunofluorescent assay. For potency in cats, each animal was inoculated intranasally with 1?ml FHV-RVG at 10^6.5 TCID₅₀. Blood samples were collected at defined intervals for antibody titration. The animals were challenged by herpes and rabies after completion of vaccination on day 180 and day 194, respectively. Our results demonstrated all vaccinated cats generated antibodies against both FHV-1 and RABV, and reached an arbitrary protective titer?>?0.5?IU/ml for rabies viral neutralizing antibody (VNA) by day 14 post inoculation (dpi) and titer peaked on 30 dpi with VNA at 24.5?±?10.23?IU/ml. All vaccinated cats presented no clinical signs of FHV-1 infection and survived rabies challenge, while the control cats had severe rhinotracheitis and died from rabies after challenge. All this demonstrated that the FHV-based recombinant vaccine is effective in protection against both FHV-1 and RABV infections.     

Safety and serological response to a matrix gene-deleted rabies virus-based vaccine vector in dogs

Dogs account for the majority of human exposures and deaths due to rabies virus (RABV) worldwide. In this report, we show that a replication-deficient RABV-based vaccine in which the matrix gene is deleted (RABV-ΔM) is safe and induces rapid and potent VNA titers after a single inoculation in dogs. Average VNA titers peaked at 3.02 or 5.11 international units (IU/ml) by 14 days post-immunization with a single dose of 10⁶ or 10⁷ focus forming units (ffu), respectively, of RABV-ΔM. By day 70 post immunization, all dogs immunized with either dose of vaccine showed VNA titers >0.5 IU/ml, the level indicative of a satisfactory immunization. Importantly, no systemic or local reactions were noted in any dog immunized with RABV-ΔM. The elimination of dog rabies through mass vaccination is hindered by limited resources, requirement for repeat vaccinations often for the life of a dog, and in some parts of the world, inferior vaccine quality. Our preliminary safety and immunogenicity data in dogs suggest that RABV-ΔM might complement currently used inactivated RABV-based vaccines in vaccination campaigns by helping to obtain 100% response in vaccinated dogs, thereby increasing overall vaccination coverage.     

酶联免疫吸附试验与中和抗体试验检测麻疹抗体比较研究

目的探讨酶联免疫吸附试验(ELISA)和中和抗体试验(NT)在麻疹抗体检测中的应用价值。方法以NT为"金标准",同时用德国Virion/Serion的定量ELISA试剂盒检测364份麻疹抗体滴度,将两种方法测定的结果进行比较。结果 NT的阳性率为57.69%,几何平均滴度(GMT)为1∶5.48,ELISA的阳性率为42.86%,平均抗体活性值为48.57IU/L。定性结果发现,ELISA特异度为99.35%,其敏感度即阳性符合率为73.81%,且阳性符合率随着滴度增加呈现增高的趋势(z=-5.99,P<0.001)。Fisher精确概率法发现,滴度1∶2组、滴度1∶4组与其他各组阳性符合率差异均有统计学意义(P<0.05),滴度1∶8组与滴度≥1∶64组阳性符合率差异有统计学意义(P<0.05),其余各组间阳性符合率差异均无统计学意义(P>0.05)。定量结果发现,ELISA抗体活性值与NT滴度呈明显正相关,相关系数r=0.884,P<0.001。结论德国Virion/Serion的定量ELISA试剂盒在检测低滴度麻疹抗体时易出现假阴性,检测高滴度麻疹抗体时,两种方法敏感性接近;滴度临界值为1∶8～1∶16。该试剂可推荐用于健康人群麻疹抗体水平监测。     

Addition of C3d-P28 adjuvant to a rabies DNA vaccine encoding the G5 linear epitope enhances the humoral immune response and confers protection

Rabies DNA vaccines based on full-length glycoprotein (G) induce virus neutralizing antibody (VNA) responses and protect against the virus challenge. Although conformational epitopes of G are the main target of VNAs, some studies have shown that a polypeptide linear epitope G5 is also able to induce VNAs. However, a G5 DNA vaccine has not been explored. While multiple doses of DNA vaccines are required in order to confer a protective immune response, this could be overcome by the inclusion of C3d-P28, a molecular adjuvant is know to improve the antibody response in several anti-viral vaccine models. To induce and enhance the immune response against rabies in mice, we evaluated two DNA vaccines based on the linear epitope G5 of Rabies Virus (RABV) glycoprotein (pVaxG5 vaccine) and another vaccine consisting of G5 fused to the molecular adjuvant C3d-P28 (pVaxF1 vaccine). VNA responses were measured in mice immunized with both vaccines. The VNA levels from the group immunized with pVaxG5 decreased gradually, while those from the group vaccinated with pVaxF1 remained high throughout the experimental study. After challenge with 22 LD50 of the Challenge Virus Strain (CVS), the survival rate of mice immunized with pVaxG5 and pVaxF1 was increased by 27% and 50% respectively, in comparison to the PBS group. Furthermore, the in vitro proliferation of anti-rabies specific spleen CD4+ and CD8+ T cells from mice immunized with pVaxF1 was observed. Collectively, these results suggest that the linear G5 epitope is a potential candidate vaccine. Furthermore, the addition of a C3d-P28 adjuvant contributed to enhanced protection, the sustained production of VNAs, and a specific T-cell proliferative response.     

An electrochemiluminescence assay for analysis of rabies virus glycoprotein content in rabies vaccines

Vaccine potency testing is necessary to evaluate the immunogenicity of inactivated rabies virus (RABV) vaccine preparations before human or veterinary application. Currently, the NIH test is recommended by the WHO expert committee to evaluate RABV vaccine potency. However, numerous disadvantages are inherent concerning cost, number of animals and biosafety requirements. As such, several in vitro methods have been proposed for the evaluation of vaccines based on RABV glycoprotein (G) quality and quantity, which is expected to correlate with vaccine potency. In this study an antigen-capture electrochemiluminescent (ECL) assay was developed utilizing anti-RABV G monoclonal antibodies (MAb) to quantify RABV G. One MAb 2-21-14 was specific for a conformational epitope so that only immunogenic, natively folded G was captured in the assay. MAb 2-21-14 or a second MAb (62-80-6) that binds a linear epitope was used for detection of RABV G. Vaccine efficacy was also assessed in vivo using pre-exposure vaccination of mice. Purified native RABV G induced a RABV neutralizing antibody (rVNA) response with a geometric mean titer of 4.2 IU/ml and protected 100% of immunized mice against RABV challenge, while an experimental vaccine with a lower quality and quantity of G induced a rVNA titer < 0.05 IU/ml and protected <50% of immunized mice. These preliminary results support the hypothesis that in vivo immunogenicity may be predicted from the in vitro measurement of RABV G using an ECL assay. Based upon these results, the ECL assay may have utility in replacement of the NIH test.     

Sero-prevalence of rubella among pregnant women in India, 2017

BackgroundWe conducted a sero-survey among pregnant women attending antenatal clinics of six hospitals which also function as sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella.MethodsWe systematically sampled 1800 pregnant women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We classified sera as seropositive (titre ≥10 IU/ml), sero-negative (titre <8 IU/ml) or indeterminate (titre 8–9.9 IU/ml) per manufacturer's instructions. In a sub-sample, we estimated the titers of IgG antibodies against rubella. IgG titer of ≥10 IU/mL was considered protective.ResultsOf 1800 sera tested, 1502 (83.4%) were seropositive and 24 (1.3%) were indeterminate and 274 (15.2%) were sero-negative. Rubella sero-positivity did not differ by age group, educational status or place of residence. Three hundred and eighty three (87.8%) of the 436 sera had IgG concentrations ≥10 IU/mL.ConclusionThe results of the serosurvey indicate high levels of rubella sero-positivity in pregnant women. High sero-prevalence in the absence of routine childhood immunization indicates continued transmission of rubella virus in cities where sentinel sites are located.     

健康成人抗百日咳毒素和抗百日咳丝状血凝素抗体检测与分析

目的评估健康成人抗百日咳毒素(anti-PT)和抗百日咳丝状血凝素(anti-FHA)抗体水平。方法选择20-59岁健康成人,采用改良ELISA(mELISA)、改良硫氰酸铵-ELISA分别测定血清anti-PT和anti-FHA IgG抗体的浓度、亲和力,分析二者的相关性;采用CHO细胞簇集试验测定anti-PT中和抗体滴度,分析与anti-PT IgG抗体浓度的相关性。结果共纳入研究对象73名,anti-PT、anti-FHA IgG抗体几何平均浓度(GMC)分别为10.4 IU/mL、58.2 IU/mL,抗体亲和力中位数分别为34.8%、61.4%,anti-PT中和抗体几何平均滴度(GMT)为1:27.3。anti-PT、anti-FHA IgG抗体的浓度与亲和力均呈正相关(r=0.45,P<0.01;r=0.76,P<0.01);anti-PT中和抗体滴度与浓度呈正相关(r=0.77,P<0.01)。结论健康成人anti-PT抗体水平较低,建议制定成人百日咳疫苗免疫程序;mELISA可替代CHO细胞簇集试验用于百日咳血清学检测。     

Association between the timing of maternal vaccination and newborns’ anti-pertussis toxin antibody levels

BackgroundPertussis remains an important global public health concern, despite the presence of extensive immunization programs. Incidence and severity of pertussis are typically higher in neonates and young infants. As a strategy to protect these young infants, maternal vaccination with Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) has been recommended in Brazil. The objective of this study was to evaluate the effects of Tdap vaccination during pregnancy on the anti-pertussis toxin (PT) IgG response in mothers and their infants at birth.Material and methodsMaternal and cord blood samples were collected from vaccinated (n = 243) and unvaccinated (n = 75) pregnant women, at the time of delivery, from July 2015 to August 2016 in São Paulo, Brazil. Anti-PT IgG antibodies were quantified by Enzyme-Linked Immunosorbent Assay (ELISA) and geometric mean concentrations (GMC) were calculated. Relationship between timing of vaccination and antibody concentrations were evaluated.ResultsMaternal and cord blood GMCs among the vaccinated group were 5.4 and 5.6 fold higher [66.5 International Units (IU)/mL and 89.8 IU/mL] compared to the unvaccinated group (12.4 IU/mL and 16.1 IU/mL), respectively (p < 0.001). Higher anti-PT IgG GMCs were observed when vaccination occurred ≥60 days before delivery compared to <60 days, suggesting that vaccination early in the third trimester may be more effective than later in pregnancy.ConclusionTdap maternal vaccination results in significantly higher anti-PT IgG in newborn infants and supports the current recommendation of the Brazilian Immunization Program.     

人工合成丙型肝炎病毒核心区多肽检测抗－HCV的初步研究

应用酶联免疫吸附试验（ＥＬＩＳＡ）检测人工合成ＨＣＶ核心区多肽（ＨＣＶ－Ｐ（２５））的抗原性，结果表明：Ｐ（２５）优于参照ＣＰ（１０）和ＳＰ序列合成的多肽片段，与美国第二代抗－ＨＣＶＥＬＩＳＡ试剂盒比较，敏感度为９２．５９％．特异度为９４．４４％，总符合率为９３．３３％。用其检测输血后肝炎，其结果与国内第二代抗－ＨＣＶＥＬＩＳＡ基本相同．但优于Ｃ１００－３．且重复性和线性均较好。因此．可单独或合并非结构区抗原用于抗－ＨＣＶ检测     

Long-term response rates of successful hepatitis B vaccination in HIV-infected patients

Background

Data on long-term response rates after successful primary hepatitis B (HBV) vaccination in HIV-infected patients are scarce.

Objective

To evaluate the durability of an effective anti-HBs titer up to 5 years after primary vaccination in a cohort of 155 HIV-infected adults.

Methods

From a previous multicenter HBV vaccination trial we selected patients with an anti-HBs titer of ≥10 IU/l 28 weeks after the first vaccination. The anti-HBs titer was measured in annually stored plasma samples up to 5 years after vaccination. Patients with decreasing anti-HBs titers <10 IU/I were defined as transient responders (TR*) and with persistent anti-HBs titers ≥10 IU/I as long-term responders (LTR^).

Results

We included 155 patients, 87 were TR and 68 LTR. Mean age, percentage of female participants and duration of HAART use at primary vaccination were similar in LTR and TR. Anti-HBs level after primary vaccination was the strongest predictor for the durability of anti-HBs. Anti-HBs >100–1000 IU/I and >1000 resulted in an OR 8.3, 95% CI 3.38–20.16; p < 0.0001 and OR 75.6, 95% CI 13.41–426.45; p < 0.0001 versus anti-HBs titer of 10–100 IU/I after primary vaccination respectively. The mean time to loss of an effective anti-HBs titer was 2.0, 3.7 and 4.4 years respectively, for patients with an anti-HBs titer of 10–100 IU/I, >100–1000 IU/I and >1000 IU/I at primary vaccination. An undetectable HIV-RNA load and use of HAART during vaccination and at follow-up were, though not significantly, associated a higher long-term persistence of an effective antibody titer.

Conclusion

The durability of an effective anti-HBs level appears to be significantly related to the height of the antibody titers after the primary immunization procedure. Schedules to improve the vaccination response in HIV-infected patients therefore seem to be justified. Whether a HBV booster is indicated remains to be elucidated.     

A prospective cohort study of immunogenicity of quadrivalent human papillomavirus vaccination among Alaska Native Children,Alaska, United States

ObjectiveIn the United States, HPV vaccination is routinely recommended at age 11 or 12 years; the series can be started at age 9. We conducted a cohort study to assess long-term immunogenicity of quadrivalent HPV vaccine (4vHPV) in an American Indian/Alaska Native (AI/AN) Indigenous population.MethodsDuring 2011–2014, we enrolled AI/AN girls and boys aged 9–14 years, who were vaccinated with a 3-dose series of 4vHPV. Serum specimens were collected at five time points: immediately prior to doses 2 and 3, and at one month, one year, and two years after series completion. Antibody testing was performed using a multiplex virus-like-particle-IgG ELISA for 4vHPV types (HPV 6/11/16/18).ResultsAmong 477 children (405 girls/72 boys) completing the 3-dose series, median age at enrollment was 11.2 years. Of the 477, 72 (15%) were tested before dose 2 and 70 (15%) before dose 3. Following series completion, 435 (91%) were tested at one month, 382 (80%) at one year, and 351 (74%) at two years. All tested participants had detectable antibody to 4vHPV types at all time points measured. Geometric mean concentrations (GMCs) for 4vHPV types at one month and two years post-series completion were 269.9 and 32.7 AU/ml for HPV6, 349.3 and 42.9 AU/ml for HPV11, 1240.2 and 168.3 IU/ml HPV16, and 493.2 and 52.2 IU/ml for HPV18. Among children tested after each dose, GMCs after doses 1 and 2 were 3.9 and 32.2 AU/ml for HPV6, 5.3 and 45.6 AU/ml for HPV11, 20.8 and 187.9 IU/ml for HPV16; and 6.6 and 49.7 IU/ml for HPV18. No serious adverse events were reported.ConclusionAll AI/AN children developed antibodies to all 4vHPV types after vaccination. GMCs rose after each dose, then decreased to a plateau over the subsequent two years. This cohort will continue to be followed to determine duration of antibody response.     

Antidiphtheria immunity of the Algerian population: a seroepidemiological study

OBJECTIVE: The antidiphtheria immunity of the Algerian population is not well known. Thus, a study was carried out on 1755 blood samples, in 1998 to better assess this vaccinal status. Three epidemics occurred in Algeria, in the years 1993, 1994, 1995, and then immunization sensitizing campaigns were introduced in September 1995. MATERIAL AND METHOD: The procedure that was used was based on the immunoenzymatic method, the reagents of which were ready for use. The interpretation of our results and vaccinal policy deduction were performed according to the VIROTECH Diphtheria ELISA technique which offers five classes in antitoxin titers: I. <0.1 IU/ml basic immunization immediately. II. 0.1-1.0 IU/ml booster immunization immediately. III. 1.0-1.4 IU/ml booster vaccination 5 years later. IV. 1.5-2.0 IU/ml booster vaccination 7 years later. V. >2.0 IU/ml booster vaccination 10 years later. RESULTS: In our series, 17.03% of the samples had a titer <0.1 IU/ml considered as insufficiently protective, an immunization was therefore recommended. 59.82% had titers ranging between 0.1 and 1 IU/ml, 5.98% had titers ranging between 1 and 1.4 IU/ml, 3.36% had titers ranging between 1.5 and 2 IU/ml, and 13.79% had titers >2 IU/ml.     

Closures and mergers of VNA home care agencies: a model for the study of causal factors

Recent closures and mergers of visiting nurses associations (VNAs) raise some potentially serious questions regarding access to home care for the elderly Medicare and Medicaid populations. While VNAs comprise less than 10 percent of the nation's certified home health agencies, they provide approximately 31 percent of all medicare home care (HCFA, 1989). In March of 1986 there were 524 visiting nurses associations nationally whereas today there remain only 495 (HCFA, 1990). A model identifying potential causes of VNA mortality is presented along with some preliminary results. VNA mortality is defined and measured by the date that Medicare certification is terminated as a result of VNA closure or merger.     

Prevalence of protective level of hepatitis B antibody 3 years after revaccination in HIV-infected children on antiretroviral therapy

After responding to highly active antiretroviral therapy (HAART), HIV-infected children had a good response to hepatitis B immunization. However, there are limited data on the durability of antibody to hepatitis B surface antigen (anti-HBs) in these children. The primary objective of this study is to determine the prevalence of protective anti-HBs level 3 years after a 3-dose HBV revaccination among HIV-infected children with immune recovery (CD4 cell ≥15%) while on HAART. The secondary objective is to assess immunologic memory among children who had waning of anti-HBs. An anti-HBs level of ≥10 mIU/mL was defined as a protective antibody level. Sixty-nine HIV-infected children who had history of a 3-dose HBV revaccination while receiving HAART were enrolled. The mean (SD) of CD4 cell and duration of HAART at time of revaccination was 27.2% (6.7) and 5.9 years (0.4), respectively. The proportion of children with protective anti-HBs level 3 years after the revaccination was 71.0% [95% CI, 58.8-81.3]. The geometric mean titer was 114(SD 5) IU/mL. By multivariate logistic analysis, the predictors for protective anti-HBs level 3 years after revaccination were CD4 cell count ≥500 cells/mm³ at the time of vaccination (p = 0.04) and anti-HBs level ≥ 100 IU/mL at 1 month after completion of the 3-dose vaccination (p < 0.001). Anamnestic response after one booster dose was demonstrated among 14 of 17 children who had waning protective anti-HBs level (82.4% [95% CI, 62.2-102.6]). Our findings support the recommendation of giving a 3-dose HBV vaccination to HIV-infected children with immune recovery while receiving HAART.     

Safety,immunogenicity, and immune persistence of two inactivated COVID-19 vaccines replacement vaccination in China: An observational cohort study

BackgroundTo mitigate a national shortage of WIBP-CorV COVID-19 vaccine, China’s regulator approved administering BBIBP-CorV after WIBP-CorV for completion of a primary series. In a pragmatic observational study, we compared immunogenicity and safety of a primary series of WIBP-CorV followed by BBIBP-CorV with a primary series of two doses of BBIBP-CorV.MethodsWe invited healthy 18–59-years-old adults who had already received either WIBP-CorV or BBIBP-CorV as their first dose in a primary series to participate in this observational cohort study. Subjects who had received WIBP-CorV as their first dose became the observation group; subjects who had received BBIBP-CorV as their first dose became the control group. All participants received BBIBP-CorV as their second dose. We obtained sera 1, 2, and 6 months after second doses for nAb titer measurement by micro-neutralization cytopathic effect assay with SARS-CoV-2 strain HB01, standardized with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Safety was assessed for the 7 days after administration of second doses.ResultsBetween March and December 2021, 275 subjects were included in the observation group and 133 in the control group. Neutralizing seropositivity (≥1:4) rates were 98.91 % and 99.25 % at 1 month and 53.16 % and 70.69 % at 6 months. One-month geometric mean titers (GMTs) were 21.33 and 22.45; one-month geometric mean concentrations (GMCs) were 227.71 IU/mL and 273.27 IU/mL. One to two months after vaccination, observation group seropositivity rates and titers were not significantly different to the control group’s. Adverse reaction rates were 11.27 % and 18.80 %, all mild or moderate in severity.ConclusionsBoth primary series were immunogenic; immunogenicity of WIBP-CorV followed by BBIBP-CorV was not different than immunogenicity following two doses of BBIBP-CorV for two months after vaccination; safety profiles were acceptable for both regimens. BBIBP-CorV can be used to complete a primary series that started with WIBP-CorV.     

Etude multicentrique de la sérologie toxoplasmique par différents réactifs ELISA commercialisés. Groupe de travail Toxoplasmose du Contr?le National de Qualité en Parasitologie.

A collaborative study conducted by the French National Agency for Quality Control in Parasitology (CNQP) and various manufacturers of ELISA kits, represented by the Association of Laboratory Reagent Manufacturers (SFRL) compared the toxoplasmosis IgG antibody titres obtained with different ELISA-IgG kits and determined the relationships between the titres obtained by these techniques and the titre defined in international units (IU). Fifty-one serum samples with toxoplasmosis antibody titres ranging from 0 to 900 IU were tested in two successive studies with 16 ELISA-IgG kits. For the negative sera, false-positive reactions were observed with one kit. For the positive sera, the titres observed in ELISA were generally higher than those expressed in IU. Above 250 IU, the very wide variability of the titres found with the different ELISA kits renders any comparative analysis impossible. For titres below 250 IU, the results are sufficiently homogeneous to permit the use of regression analysis to study how the results for each ELISA kit compare with the mean results for the other kits. The slope of the line of regression shows a tendency to over-titration or under-titration compared with the results of the other manufacturers; the ordinate at the origin reflects the positivity threshold of the reaction and can be used to assess the risk of a lack of sensitivity (high threshold) or of specificity (threshold too low). On the whole, the trends revealed for a given manufacturer are constant from one study to the other. Within this range of titres, regression analysis also reveals the general tendency of ELISA kits to overestimate the titres by comparison with immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)     

A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated regimen

BackgroundHuman Rabies infection continues to be potentially fatal despite the availability of post-exposure prophylaxis with rabies vaccine. The PIKA Rabies vaccine adjuvant is a TLR3 agonist and has been shown to be safe and immunogenic in clinical phase I studies.MethodsWe conducted a phase II, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA rabies vaccine under an accelerated regimen. 126 subjects were randomized into two groups: control vaccine classic regimen (“control-classic”) and PIKA vaccine accelerated regimen (“PIKA-accelerated”). Subjects were followed up for safety and rabies virus neutralizing antibodies (RVNA).ResultsBoth the control and PIKA vaccines were generally well tolerated. 57.6% of subjects in the PIKA vaccine group, compared with 43.8% of subjects in the control-classic group, achieved the target RVNA titer of ≥0.5 IU/mL by Day 7. All subjects achieved the target RVNA titer by Day 14. The RVNA geometric mean titer at Day 7 was 0.60 IU/ml in the PIKA vaccine group and 0.39 IU/ml in the control-classic group. At Day 14, the RVNA geometric mean titer was 18.25 IU/ml in the PIKA-accelerated group and 19.24 IU/ml in the control-classic group. The median time taken to reach the target RVNA titer level of ≥0.5 IU/mL was 7.0 days (95% CI: 7.0–42.0 days) in the PIKA-accelerated group and 14.0 days (95% CI: 7.0–42.0 days) in the control-classic group.ConclusionThe accelerated regimen using the investigational PIKA Rabies vaccine was well-tolerated and demonstrated non-inferior immunogenicity compared to the classic regimen using the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov (NCT02956421).     

Cholecalciferol supplementation to improve the hepatitis B vaccination response in hemodialysis patients: A first randomized open label pilot study (DeVitaHep)

BackgroundPatients with advanced chronic kidney disease should be vaccinated against hepatitis B. In observational studies vitamin D insufficiency is associated with a reduced seroconversion rate. The effect of cholecalciferol supplementation on hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency is unknown.MethodsIn this randomized open label pilot study 40 unvaccinated haemodialysis patients with 25(OH)D insufficiency (<30 ng/mL) were enrolled. In the supplementation group, we administered cholecalciferol orally in a dose of 28,000 IU weekly for a maximum of 12 weeks. Hepatitis B vaccination (HBvaxPRO 40 µg i.m. months 0, 1, 6) was performed after achieving a 25(OH)D level >30 ng/mL or after completing three months of supplementation despite failure to achieve the target level. In the control group, patients were vaccinated immediately after randomization. Anti-hepatitis B-antibody titer (anti-HBs) was measured eight weeks after completing the vaccination course.ResultsThirty-seven (26 male, 11 female) patients aged 65 (13.5) years underwent randomization with 17 patients allocated to the control group and 20 patients included in the supplementation group. After 12 weeks of cholecalciferol supplementation, mean (SD) 25(OH)D concentration increased from 15.0 (8.0) to 31.0 (7.1) ng/mL, but remained unchanged in the control group (14.0 (7.1) to 11.6 (7.5) mg/mL). Neither the number of patients with seroconversion (anti-HBs titer ≥ 10 IU/L; n = 6 (35.3%) vs n = 3 (27.3%), p = 0.704), nor the number of patients with seroprotection (anti-HBs titer >100 IU/L; n = 4 (23.5%) vs n = 2 (18.2%) differed between treatment groups. Cholecalciferol supplementation was safe without treatment-related adverse events.ConclusionIn this small pilot study, high-dose oral cholecalciferol supplementation did not improve the hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency.This clinical trial was registered within EudraCT (EudraCT number 2011-004621-26).     

Rubella virus-specific humoral immune responses and their interrelationships before and after a third dose of measles-mumps-rubella vaccine in women of childbearing age

In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks).We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5 years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10 IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT₅₀ (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150 IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (≥4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses.