Neutralizing antibody response after intradermal rabies vaccination in hemodialysis patients

Abnormal immune function in chronic hemodialysis (HD) patients could impair immunologic responsiveness to various vaccinations. Such inadequate response makes the HD patients to be at risk of certain fatal but preventable diseases including rabies. Although the effectiveness of rabies vaccination has been established in healthy subjects, the responsiveness of the current rabies vaccination has never been examined in HD patients. The effectiveness of post-exposure rabies vaccine was assessed in 20 stable thrice-a-week chronic HD patients who received adequate dialysis and did not have history of rabies vaccination during the last 20 years. All participants received the standard intradermal Thai Red Cross post-exposure rabies vaccination. Blood samples were obtained for determination of rabies neutralizing antibody (Nab) before the first dose (day 0) and on days 14 and 90 after vaccination. Prior to simulated vaccination, six of twenty patients already had Nab titers above the protective levels of 0.5 IU/mL while the remaining fourteen patients showed undetectable Nab. All subjects reached Nab titers above 0.5 IU/mL(acceptable level for rabies protection) by days 14 after vaccination. The geometric mean titers (GMTs) on days 14 after vaccination were 3.2 + 3.1 IU/mL (range 0.81–9.17 IU/mL). At day 90 after vaccination, 13 of 14 patients had Nab titers above the protective levels, resulting in the response rate of 92.8%. The GMTs of Nab on day 90 after vaccination were 5.09 + 1.79 IU/mL (0.42–25.0 IU/mL). There were no correlations between Nab titers and patient characteristics. No serious adverse reactions were detected. In conclusion, chronic HD patients receiving adequate dialysis have excellent protective immunological response after intradermal post-exposure rabies vaccination as WHO recommendation.     

The immune response to rabies virus infection and vaccination

Infection with rabies virus causes encephalitis in humans that has a case fatality rate of almost 100%. This inability to resolve infection is surprising since both pre-exposure vaccination and, if given promptly, post-exposure vaccination is highly effective at preventing encephalitic disease. The principal immunological correlate of protection produced by vaccination is neutralizing antibody. T-helper cells contribute to the development of immunity whereas cytotoxic T cells do not appear to play a role in protection and may actually be detrimental to the host. One reason for a failure to protect in humans may be the poor immunological response the virus provokes, despite the period between exposure to virus and the development of disease being measured in months. Few individuals have measurable neutralizing antibody on presentation with disease, although in many cases this develops as symptoms become more severe. Furthermore, when antibody is detected in serum it rarely appears in cerebrospinal fluid suggesting limited penetration into the CNS, the site where it is most needed. The role of the modest mononuclear cell infiltrate into the brain parenchyma is unclear. Some studies suggest the virus can suppress cell-mediated immunity early during the infection although there is little mechanistic evidence to support this beyond suppression of intracellular interferon production by the viral phosphoprotein. In contrast, levels of antibody in the CNS correlate to the peak virus production within the CNS. Here we review the current understanding of immune responses to rabies infection and vaccination against this disease. This article identifies a need to understand how rabies antigens are initially presented and how this can influence the subsequent development of antibody responses. This could help identify ways in which the response to prophylactic vaccination can be enhanced and how the natural immune response to infection can be boosted to combat neuroinvasion.     

Immunogenic response in obese patients undergoing rabies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination

BackgroundObesity is a risk factor for increased morbidity and mortality associated with many vaccine preventable infectious diseases such as influenza. Moreover, higher volume of passive rabies immunoglobulin (RIG) due to weight based dosing might suppress vaccine-induced immune responses in obese patients. This study aimed to evaluate the effect of obesity on humoral immune responses to combined equine RIG and rabies vaccine treatment among patients with WHO category III exposure to a rabies suspected animal.MethodsA single centre, prospective, open-labelled study among WHO category III rabies exposed patients was conducted to compare serum rabies virus neutralizing antibody (RVNA) responses measured by rapid fluorescent focus inhibition test between obese (body mass index, BMI > 30 kg/m²) and control (BMI < 25 kg/m²) patients after combined immunization with equine rabies immunoglobulin and purified chick-embryo cell rabies vaccine for post exposure prophylaxis treatment.ResultsPost-vaccination geometric mean titer (GMT) of RVNA concentrations between two groups at day 7 were 0.33 (95% CI: 0.23, 0.46) vs 0.39 (95% CI: 0.27, 0.55), 4.61 (95% CI: 3.20, 6.63) vs 3.78 (95% CI: 2.77, 5.16) at day 14, and 7.45 (95% CI: 5.86, 9.49) vs 5.93 (95%CI: 4.46–7.90) at day 28 for obese and control patients, respectively. There was no statistically significant difference of RVNA GMT between two groups. Seroconversion to at least adequate concentration (RVNA titer ≥0.5 IU/mL) rates were 34% at day 7 and 100% at days 14 and 28 in both groups. There were no immediate hypersensitivity reaction and no serious adverse events observed during the study period.ConclusionsThere was no evidence of immunosuppression of antibodies’ responses in obese patients. Combined ERIG and rabies virus vaccination for post exposure treatment is safe.     

2013-2016年天津市狂犬病暴露后免疫效果分析

目的 了解天津市狂犬病暴露后免疫者血清中和抗体水平,为指导狂犬病预防控制工作提供科学依据。方法 对2013-2016年在天津市疾病预防控制中心动物致伤门诊全程注射狂犬病疫苗并于免疫后14～30天采血进行快速荧光灶抑制试验者进行统计学分析。结果 不同月份接种狂犬病疫苗,中和抗体水平趋于平稳,在10IU/ml上下波动;未成年组头面部暴露比例最高,青壮年组下肢暴露比例最高,老年组上肢暴露比例最高;91例暴露后免疫者血清中和抗体几何平均滴度为9714IU/ml,阳转率为100%;女性中和抗体水平明显高于男性(t=2482,P=0015);复种组中和抗体水平远高于初种组(疫苗组及疫苗+蛋白组)(F=5356,P=0006);不同年龄组、不同暴露部位、不同暴露等级及接种不同疫苗中和抗体水平无统计学差异(P皆＞005)。结论 狂犬病暴露后免疫效果不受季节、年龄、暴露部位、暴露等级及接种疫苗种类影响,女性免疫效果优于男性,复种组免疫效果明显优于初种组。     

A single center,open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults

In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1 mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1 ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1 mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14–21 days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naïve and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160 days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1 mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic.     

Safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults

In the present pilot study, intradermal ID delivery systems with a BD microneedle from 1 to 3 mm in length, and epidermal delivery (BD skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. Circulating neutralizing antibodies were measured against the rabies virus after the Vero cells rabies vaccine was administered at D0, D7, D21 and D49. This clinical evaluation in 66 healthy volunteers shows that ID delivery using BD microneedle technology of 1/4 the IM antigen dose is safe, efficient and reliable, resulting in a protective seroconversion rate. In contrast, the epidermal delivery route did not produce an immune response against the rabies vaccine.     

酶联免疫法筛查人类免疫缺陷病毒抗体在艾滋病诊断中的应用

目的 探讨酶联免疫法筛查人类免疫缺陷病毒(HIV)抗体在艾滋病诊断中的应用效果.方法 选择2019年1—12月于医院接受HIV抗体筛查的1000例艾滋病疑似患者作为研究对象,所有患者均行酶联免疫法与金标斑点法检测,以初筛及印证试验联合诊断结果 为金标准,比较酶联免疫法与金标斑点法的诊断准确度、灵敏度、特异度.结果 酶联...     

Modification of AxSYM Human Immunodeficiency Virus Assay to Identify Recent Human Immunodeficiency Virus Infections in Korean Human Immunodeficiency Virus-Positive Individuals

Objectives

To estimate human immunodeficiency virus (HIV) incidence using HIV avidity assays in Korea, we established a serological testing method to differentiate recent HIV infections from long-standing ones.

Methods

We adopted two incidence assays, the BED HIV-1 incidence test (Calypte Biomedical) and an HIV avidity assay (using Abbott AxSYM HIV Antigen/Antibody Combo), and performed them on Korean HIV samples obtained from 81 HIV seroconverters (n = 193), 135 HIV-positive samples, and three HIV commercial incidence panels (PRB965, PRB933, and PRB601 from SeaCare). To determine the most optimal concentration of the chaotropic agent (Guanidine) and the cutoff value for the avidity assay, we evaluated the sensitivity and specificity of the assay at different concentration levels.

Results

We determined that the concentration of Guanidine to be used in the avidity assay was 1.5M. The cutoff value of the avidity index (AI) was 0.8, and the sensitivity and specificity were 90.2% and 83.8%, respectively, under this condition. The gray zone for the avidity assay was 0.75–0.85 AI. The mean of coefficient of variation was low, at 5.43%.

Conclusion

An optimized avidity assay for the diagnosis of recent HIV infections using Korean samples was established. This assay will be applied to investigate the level of recent infection and will provide basic data to the HIV prevention policy in Korea.     

Psychometric validation of the revised Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) quality of life instrument

The revised Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) quality of life (QoL) instrument has been updated and expanded to provide more complete and accurate coverage of human immune deficiency virus/ acquired immune deficiency syndrome (HIV/AIDS)-related QoL. Factor analysis and the Rasch measurement model were used to determine a new subscale structure for the FAHI. The content of these subscales, including physical well-being (ten items, = 0.91), function and global well-being (13 items, = 0.86), emotional well-being/living with HIV (10 items, = 0.82), social well-being (eight items, = 0.73), and cognitive functioning (three items; = 0.75), reflect both general illness- and HIV/AIDS-specific QoL concerns: a total QoL score can also be calculated for the FAHI (44 items, =0.91). Psychometric evaluation revealed good internal consistency reliability for the FAHI and its subscales. In addition, construct validity, known groups validity and sensitivity to change were demonstrated by significant associations between the FAHI and additional indicators of functional status, psychological symptoms, stress and illness severity. In summary, the FAHI is a psychometrically sound instrument that captures multiple important dimensions of HIV/AIDS-related QoL. It is brief, easy to administer and score, has been translated into nine languages other than English and is appropriate for use in clinical trials and clinical practice.     

Antibody response of patients after postexposure rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or purified Vero cell rabies vaccine

Although the introduction of tissue culture vaccines for rabies has dramatically improved the immunogenicity and safety of rabies vaccines, they are often prohibitively expensive for developing countries. To examine whether smaller doses of these vaccines could be used, we tested the safety and immunogenicity of purified chick embryo cell vaccine (PCECV) on 211 patients in Thailand with World Health Organization (WHO) category II and III exposures to rabies. The patients presented at two Thai hospitals and were randomized into three groups. Patients in Group 1 received 0.1 ml PCECV intradermally at two sites on days 0, 3, 7, and at one site on days 30 and 90. Group 2 was treated similarly, except that purified Vero cell rabies vaccine (PVRV) was used instead of PCECV. Group 3 received 1.0 ml PCECV intramuscularly on days 0, 3, 7, 14, 30 and 90. After 0, 3, 7, 14, 30 and 90 days serum was collected from the subjects and the geometric mean titres (GMTs) of rabies virus neutralizing antibody determined. After 14 days the GMT of 59 patients vaccinated intradermally with PCECV was equivalent to that of patients who received PVRV. Adverse reactions were more frequent in patients who received vaccines intradermally, indicating the reactions were associated with the route of injection, rather than the vaccine per se. We conclude that PCECV is a safe and highly immunogenic vaccine for postexposure rabies vaccination when administered intradermally in 0.1-ml doses using the two-site method ("2,2,2,0,1,1") recommended by WHO.     

1994～2009年玉溪市流动人口艾滋病病毒感染情况分析

[目的]分析玉溪市流动人口中艾滋病疫情状况,为制定预防艾滋病传播的策略和措施提供依据。[方法]对1994~2009年玉溪市流动人口中艾滋病疫情报告资料进行描述性分析。[结果]1994~2009年玉溪市累计报告艾滋病病毒(HIV)感染者和艾滋病病人2 660例,其中流动人口450例,占16.92%;外地户籍、本地户籍者分别占6.9%、10.0%。450例流动人口的HIV感染者和艾滋病病人中,男性占57.33%,文化程度初中及以下者占86.22%,已婚有配偶者占48.89%,农民工、从事服务行业者分别占46.89%、21.78%;传播途径为异性传播的占55.11%,注射吸毒传播的占28.00%,男男同性传播、母婴传播、输血/血制品传播的分别占2.00%、1.33%、0.22%。[结论]玉溪市流动人口艾滋病疫情比较严重。     

Changes in Human Immunodeficiency Virus-related Knowledge and Stigmatizing Attitudes among Korean Adolescents from 2006 to 2011

ObjectivesThis study assessed the prevalence and changes of human immunodeficiency virus (HIV) knowledge and stigmatizing attitudes in 2006, 2008, and 2011.MethodsThree cross-sectional surveys were conducted in 2006, 2008, and 2011. A cross-sectional sample of high school students in Seoul, South Korea was targeted. A self-administered questionnaire measuring general and transmission and discriminatory attitudes was used.ResultsMisconceptions about casual contact were widespread, even though the proportion responding incorrectly decreased significantly over the 5-year period. The respondents in all surveys displayed a high level of discrimination against those with HIV/AIDS in some situations, particularly in the idea of HIV/AIDS making the respondent feel disgusted (63.3% in 2006, 57.5% in 2008, and 52.6% in 2011), avoiding sitting with people with HIV/AIDS (50.6% in 2006, 50.5% in 2008, and 48.5% in 2011), and blaming those with HIV for becoming infected (46.6% in 2006, 42.8% in 2008, and 43.0% in 2011). Even though respondents had a high level of stigmatizing attitudes, the survey showed that the stigma has declined over the 5-year period.ConclusionThe survey results showed that public health policy should recognize that HIV stigmatizing attitudes persist in Korea. This finding has implications for the development of intervention programs focusing on reducing the levels of discrimination.     

Operational performance and analysis of two rabies vaccination campaigns in N’Djamena,Chad

Transmission of rabies from animals to people continues despite availability of good vaccines for both human and animal use. The only effective strategy to achieve elimination of dog rabies and the related human exposure is to immunize dogs at high coverage levels. We present the analysis of two consecutive parenteral dog mass vaccination campaigns conducted in N’Djamena in 2012 and 2013 to advocate the feasibility and effectiveness for rabies control through proof of concept. The overall coverage reached by the intervention was >70% in both years. Monthly reported rabies cases in dogs decreased by more than 90% within one year. Key points were a cooperative collaboration between the three partner institutions involved in the control program, sufficient information and communication strategy to access local leaders and the public, careful planning of the practical implementation phase and the effective motivation of staff.The dynamic and semi to non-restricted nature of dog populations in most rabies endemic areas is often considered to be a major obstacle to achieve sufficient vaccination coverage. However, we show that feasibility of dog mass vaccination is highly dependent on human determinants of dog population accessibility and the disease awareness of dog owners. Consequently, prior evaluation of the human cultural and socio-economic context is an important prerequisite for planning dog rabies vaccination campaigns.     

Single-visit, 4-site intradermal (ID) rabies vaccination induces robust immune responses 5 years after 1-week, 4-site ID primary post-exposure prophylaxis in the Philippines

BackgroundIn a randomized controlled study (NCT01622062) a 1-week, 4-site intradermal (ID, 4-4-4-0-0) post-exposure prophylaxis (PEP) rabies vaccination regimen with purified Vero cell rabies vaccine (PVRV, Verorab®, Sanofi Pasteur), either without (Group 1) or with (Group 2) purified equine rabies immunoglobulin (ERIG), patients in the Philippines achieved seroconversion rates at Day 14 that were non-inferior to that of the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with ERIG (Group 3). Presented here are the annual immunogenicity data up to five years after the last primary dose, and the immunogenicity and safety data following simulated PEP with single-visit, 4-site ID regimen.MethodsRabies virus neutralizing antibodies (RVNA) were determined by rapid fluorescent focus inhibition test (RFFIT). Participants (n = 397) received simulated PEP vaccination ID at Year 5 and RVNAs were assessed at Day 11 post-vaccination.ResultsSeroconversion rates (RVNA titres ≥ 0.5 IU/mL) during annual follow-up remained >95% in Group 1 and were relatively stable at 80–90% in Group 2, but decreased from 80% to 64% in Group 3. RVNA geometric mean titres (GMTs) in Group 1 were consistently higher than in the other two groups, and those in Group 3 were generally lower than in the other two groups. There was a clear anamnestic response to vaccination in all groups, with all participants achieving RVNA titres ≥ 0.5 IU/mL at Day 11 post-simulated PEP booster vaccination. There were no safety concerns raised during annual follow-up and with simulated post-exposure vaccination with PVRV.ConclusionThe shortened, 1-week, 4-site ID regimen with PVRV achieved persistently higher RVNA titres than the updated 2-site TRC regimen, and more participants remained seroprotected up to five years after the last dose of primary immunization. Simulated post-exposure with 4-site ID rapidly induced an anamnestic response indicative of robust protection.     

Assessing the immunological response to hepatitis B vaccination in HIV-infected patients in clinical practice

Hepatitis B vaccination is recommended in HIV-infected patients. Achieving seroprotection rates (anti-HBs ≥ 10I U/L) comparable to the general population remains a challenge. The aim of this study was to analyze the proportion of responders among patients infected with HIV receiving primary HBV vaccination and identify factors associated with seroprotection rates. We analyzed the response to vaccination (antiHBs titers) in 474 HIV-infected patients receiving ≥ 1 doses of vaccine between 1994 and 2009. Factors associated with response to vaccination were analyzed using a logistic regression model. Considering the first vaccine courses administered, a response rate of 60.3% (286/474) was obtained. Eighty-seven patients began a second course, responding in 58.6% of cases. Regardless of the number of doses, schedules, and whether or not they completed the course, the response rates were 71.1% (337/474). After adjustment for year of reception of the first dose, responders were less likely to have a higher baseline HIV 1-RNA viral load (OR: 0.78 95% CI: 0.68-0.91) and more likely to have a CD4 count ≥ 350 cells/μL (OR: 1.64, 95% CI: 1.03-3.62). Patients receiving less than three doses of vaccine (OR: 0.31 95% CI 0.15-0.61) or three doses of the rapidly accelerated schedule (OR: 0.35 95% CI 0.15-0.81) had a lower probability of response in comparison with those receiving three doses of an accelerated schedule. In patients diagnosed with HIV, HBV vaccination before evolution to greater immunosuppression (CD4 < 350 cells/μL) or delaying vaccination until the CD4 count is higher could provide better seroprotection rates. The rapidly accelerated vaccination schedule should be used with caution, due to its lower effectiveness. If seroprotection is not achieved after the first course, revaccination seems to be effective in increasing the proportion of responders.     

2009年黔南地区229例HIV抗体阳性者复检结果

[目的]通过对艾滋病毒（HIV）抗体初筛检测和复检确认,一定程度上了解黔南地区艾滋病（AIDS）分布特征、传播途径及发展规律,为制定防控措施提供依据。[方法]采用酶联免疫双抗原夹心法试验,由基层检测单位对各类人员进行HIV抗体初筛检测,对初筛阳性穆不确定者重新采血送黔南州疾控中心复检确认。[结果32009年在黔南地区检出并确认HIV抗体阳性者229例,也即HIV感染者229例。感染者的年龄为2～81岁,以30岁及以下中青年为主;性别比男性占64．63％,女性占35．37％;民族分布有汉、布依、水、苗、侗、土家、壮、仡佬8个民族,以汉族最多119例,占51．97％;文化程度以初中比例为最高132例．57．64％。[结论]黔南地区艾滋病感染已向各类人群扩散,需加强相应的防控措施。     

Immunogenicity and safety of two-visit,intradermal pre-exposure rabies prophylaxis simultaneously administrated with chimeric live-attenuated Japanese encephalitis vaccine in children living in rabies and Japanese encephalitis endemic country

BackgroundReducing the number of doses required for pre-exposure prophylaxis (PrEP) would make it more feasible and cost-effective to implement in children at the highest risk of rabies exposure in Asia. We studied immune response of 2-site intradermal (ID) injection of rabies vaccine on days 0 and 28 for rabies PrEP simultaneously administrated with live-attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) for children living in endemic area.Research design and methodsSeronegative children (n = 49) aged 12–16 months were randomized 2:1 into two groups: Group A subjects were vaccinated with 0.1-mL ID injection of purified Vero cell rabies vaccine (PVRV), each at two sites on day (D) 0 and D28; Group B subjects were vaccinated with conventional 0.5-mL intramuscular PVRV on D0, D7 and D28. Both groups received one dose of JE-CV subcutaneously on D0 and D365. Rabies virus neutralizing antibody (RVNA) titers were measured on D0, D42 and D365 after vaccination; Japanese Encephalitis (JE) neutralizing antibody titers were determined on D0, D42, D365 and D379.ResultsAll children had RVNA ≥ 0.5 IU/mL on D42 (geometric mean titers [GMTs] of RVNA 14.35 IU/mL [Group A] and 14.83 IU/mL [Group B], p > 0.05]). On D365, RVNA GMTs of subjects in group A and B were 1.50 IU/mL and 2.00 IU/mL (p > 0.05), respectively. All children had seroprotection following booster dose of JE-CV. There were no vaccine-related SAEs observed.ConclusionThe 2-site ID PrEP with PVRV on days 0 and 28 co-administrated with JE-CV are safe and immunogenic.