动物致伤人群接种狂犬病疫苗后血清学与流行病学效果的初步分析

目的观察就诊的动物致伤者,分别全程足量接种两种剂型狂犬病疫苗后,其血清中抗体阳转率和疫苗保护率。方法2000—2001年就诊者全程接种浓缩苗,2002—2003年的全程接种精制纯化(vero细胞)苗。严重致伤者,于0、3天接种加倍量疫苗,并于0天的同时,对其伤口周围用抗狂犬病血清(40IU/kg)进行浸润注射。联合使用抗血清者,完成全程5次注射后第15、75天各加强1针疫苗。接种结束后15—20天,以间接混合酶标法检测血清中抗狂犬病病毒抗体。期内经疫情报告系统,收集当年观察人群狂犬病病例,计算两接种组人群的发病率,并分别与当年未接种疫苗的动物致伤人群比较,以估算疫苗保护率。结果4年中该人群抗体总阳性率为95.60%。接种精制纯化苗组的阳性率为96.37%,高于浓缩苗组的94.83%。狂犬病疫苗保护率,精制苗1年和2年的均为100.00%;浓缩苗1年的为95.46%,2年、3年和4年的为90.91%。结论动物致伤人群规范处理局部伤口后,及时全程接种狂犬病疫苗,其抗体阳性率较高。国产精制纯化苗接种人群的抗体阳性率和1~2年的疫苗保护率高于浓缩苗。从我国狂犬病防治工作实际出发,提示国产精制纯化苗需尽快降低成本,以巩固和提高其接种率。     

浙江省肾综合征出血热(HFRS)-Ⅰ型鼠脑纯化疫苗安全性、血清学、防病效果和免疫策略研究

目的　现场观察、考核兰州生物制品研究所生产的HFRS -Ⅰ型鼠脑纯化疫苗的安全性、血清免疫学与防病效果 ,并确定其免疫程序和免疫策略。方法　试验组和对照组按随机整群分组法进行分组 ;采用 0、7、2 8d及免后 1年加强 1针的免疫程序 ;分别采集免前、全程接种后 2周、加强前、加强后两周、加强后 1、2、3、4、5年的部分接种者全血和微量耳垂血 ,分别测定其中和抗体和IFA抗体 ,观察疫苗的血清免疫学效果和现场流行病学防病效果。结果　在 1995年 8月～ 2 0 0 1年 12月的 6年时间里从疫苗开始接种到加强后 5年 ,观察了HFRS -Ⅰ型鼠脑灭活纯化疫苗的安全性、血清免疫学效果和流行病学防病效果等。纵观结果 :证明该疫苗除了因疫苗中残留蔗糖导致较重较普遍的局部反应外 ,未发现其他严重的副反应 ,证明疫苗有较好安全性。从血清免疫效果看 ,86例全程接种后两周的免疫者血清 ,IFA抗体阳转率达 10 0 % ,中和抗体阳转率为4 4 4 4 % (8/ 18)。 1年后 ,IFA抗体和中和抗体阳性率分别下降到 2 8 5 7%和 14 80 %。但加强后 2周的血清IFA抗体和中和抗体阳性率分别反弹至 83 33%和 5 5 5 6 % ,其抗体几何平均滴度也随之回升 ,但不十分明显。此外 ,在加强后 2年IFA和中和抗体阳性率再次下降到较低水平 ,分别为     

狂犬病疫苗接种人群中狂犬病病毒中和抗体水平分析

目的 通过分析狂犬病疫苗接种人群中狂犬病病毒RABV中和抗体特征,为狂犬病防控提供依据。方法 收集2019-2020年杭州市职业病防治院犬伤后暴露预防接种门诊抗体检测者信息,经筛选后确定157例RABV中和抗体检测者作为研究对象,采用快速荧光灶抑制试验检测狂犬病毒中和抗体,利用横断面研究方法对狂犬病毒中和抗体水平进行人群特征分析。结果 研究对象中,初种者98人,复种者59人,复种者中2-1-1程序比5针法产生的抗体水平更高,其余特征均无统计学差异(P>0.05)。除1例初种者中和抗体效价低于0.5 IU/mL,其余检测者中和抗体效价均高于0.5 IU/mL。狂犬病毒中和抗体水平时间趋势分析显示,狂犬病毒中和抗体水平与时间呈负相关,回归方程为(F=4.974,P=0.031),标准化回归系数为-0.322(t=-2.230,P=0.031)。结论 复种者狂犬病毒中和抗体水平与免疫程序有关,2-1-1程序对人体再次免疫应答的效果优于5针法。接种疫苗2年后部分个体出现失保护状态,再次暴露有必要全程接种狂犬病疫苗。     

5119例狂犬病疫苗全程免疫接种者血清抗体水平检测结果分析

目的了解狂犬病疫苗全程免疫后抗体产生情况及其影响因素,为狂犬病疫苗预防接种工作提供依据。方法采用ELISA法对5119例于我院全程接种狂犬病疫苗者进行抗狂犬病病毒抗体检测并分析结果。结果5119份血清标本中抗体阳性5035份,总阳性率98．36％。其中男性及女性阳性率分别为97．91％、98．75％;P〈0．05。0—19岁、20～59岁及〉60岁者抗体阳性率分别为99．3％、98、4％、96．3％,两两比较,P均〈0．05;即随着年龄增大,接种疫苗后抗体阳性率呈下降趋势。结论性别对狂犬疫苗接种后抗体的产生有影响;随着年龄的增长,注射疫苗后抗体阳性率逐渐下降。对接种后抗体阴性者应再次进行全程免疫。     

BCG-CpG-DNA佐剂人用狂犬病疫苗(MRC-5细胞)在食蟹猴体内的免疫原性

目的 评价BCG-CpG-DNA佐剂人用狂犬病疫苗(MRC-5细胞)在食蟹猴体内的免疫原性。方法 将食蟹猴随机分为对照组、3针组及4针组,经后肢肌肉免疫,1.0 mL/剂。3针组及4针组均接种BCG-CpG-DNA佐剂人用狂犬病疫苗,3针组于0 d、7 d、21 d各接种1剂,4针组于0 d、3 d、7 d、14 d各接种1剂;对照组接种市售国产同类疫苗,于0 d注射2剂、7 d及21 d各1剂。初免前(0 d)及初免后7 d、14 d、28 d、35 d、49 d、63 d后肢隐静脉采血,分离血清及外周血淋巴细胞。快速荧光灶抑制实验(Rapid Fluorescent focus Inhibition Test, RFFIT)及酶联免疫斑点检测技术(Enzyme-linked Immunospot Assay, ELISPOT)分别检测血清中抗狂犬病病毒中和抗体水平和外周血淋巴细胞中细胞因子IFN-γ、IL-2的表达水平。结果 食蟹猴血清中和抗体水平于免疫前均呈阴性(抗体效价<0.5 IU/mL),3针组和对照组在初免后7～28 d呈上升趋势,于28 d达最高,4针组在14 d...     

肾综合征出血热I型疫苗中期流行病学效果研究

目的：观察肾综合征出血热I型灭活疫苗在浙江省肾综合征出血热高发疫区大面积人群接种后的安全性,考核流行病学防病效果。方法 采用IFAT法测特异性IgG抗体,用MCPENT法测中和抗体滴度。结果 共接种10460人,全程接种者占97.30%,对照16159人。全程接种后2周荧光抗体阳转率为100.00%(67/67),中和抗体阳转率为44.44%,几何平均滴度分别为72.14%和4.63。加强免疫后血清抗体迅速回升,1年后又逐渐下降。预防接种后全身反应和局部反应轻微。接种组无发病,对照组发病24例,死亡3例。疫苗中期（基础免疫后4年）流行病学防病效果良好,人群保护率达100%（95%可信区间为96.3%～100%）。结论 HFRS疫苗安全性良好,中期流行病学防病效果明显,取得了良好的经济和社会效益。     

国产冻干无佐剂Vero细胞狂犬病疫苗接种效果观察

目的观察狂犬病暴露前人群应用国产冻干无佐剂Vero细胞狂犬病疫苗小剂量皮内注射的接种反应及其免疫原性。方法选择犬密切接触人群,按照知情自愿的原则,对244名Ⅰ级狂犬病暴露者接种国产纯化冻干无佐剂Vero细胞狂犬病疫苗(PVRV),按照随机、单盲的原则分成两组,A组122人,分别于第0、7、28 d皮内注射,每个部位0.1 ml;B组122人,分别于第0、7、28 d全量(0.5 ml)PVRV三角肌注射。观察受种者疫苗注射部位皮内及肌肉局部和全身反应,采用间接ELISA法检测血清抗体。结果皮内注射组局部红肿、硬结、疼痛、瘙痒,发生率分别为1.09%、0.27%、0.27%和10.66%,肌肉注射组分别为0.82%、0.27%、1.64%和0.82%。皮内注射组发热、皮疹、头痛、疲劳乏力等全身反应发生率分别为0.27%、0.27%、0.55%和0.82%,肌肉注射组分别为0.55%、0.27%、0.55%和0.82%。不良反应常发生在第1、第2次注射之后。皮内注射(ID)组、肌肉注射(I M)组接种狂犬病疫苗后42 d抗体阳转率分别是94.21%和95.08%,差异无统计学意义(P0.05)。结论国产冻干Vero细胞狂犬病疫苗免疫原性良好,皮内、肌肉注射不良反应轻微。对暴露前人群小剂量皮内注射国产冻干无佐剂Vero细胞狂犬病疫苗是可行的。     

慢性HBV感染者接种新型冠状病毒疫苗的安全性及有效性研究

目的?分析慢性HBV感染者全程接种3剂新型冠状病毒（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）疫苗的安全性及有效性。方法?纳入2021年10月—2022年8月在解放军总医院第五医学中心就诊并自愿接种SARS-CoV-2疫苗的慢性HBV感染者107例，在第0（基线）、1、2、4、7、8月时进行访视并定期检测血常规、血生化及凝血四项等实验室指标。通过记录慢性HBV感染者接种每剂SARS-CoV-2疫苗后28 d内的不良反应及实验室指标的动态变化特点以评估其安全性。在随访时留取血浆样本检测中和抗体滴度以评估其有效性，同时分析抗体滴度可能的影响因素。结果?慢性HBV感染者接种3剂SARS-CoV-2疫苗后不良反应发生率依次为22.43%（24/107）、19.79%（19/96）和16.67%（12/72），最常见的局部不良反应为接种部位疼痛，最常见的全身性的不良反应为疲劳、乏力；接种疫苗后生化学及病毒学指标未出现恶化；接种每剂SARS-CoV-2疫苗后中和抗体滴度均显著上升（P均＜0.05），而后随着时间逐渐下降；抗体阳性组受试者年龄低于阴性组受试者[（42.27±9.40）岁 vs. 48.00（43.00，53.50）岁，P = 0.040]。结论?慢性HBV感染者接种SARS-CoV-2疫苗后具有良好的安全性及有效性，不良反应发生率低且未发生疫苗相关严重不良事件；接种第3剂加强针后产生的中和抗体反应最为强烈；而年龄则会影响慢性HBV感染者接种疫苗后的抗体滴度。     

日本脑炎病毒DNA疫苗和基因工程亚单位颗粒疫苗的动物保护实验研究

目的　评价 3种日本脑炎病毒 (JEV)新型疫苗 ,即E蛋白病毒样颗粒 (VLPs)、DNA疫苗 (pV/JE)以及E蛋白颗粒 (Eps)的动物免疫效果。方法　BALB/c小鼠经 2次接种疫苗后 ,测定其病毒特异性的CTL活性、结合抗体、中和抗体 ,并以10LD5 0JEV攻击免疫小鼠 ,观察其保护效果。结果　各新型疫苗组的CTL活性为 33%～ 5 6 % ,灭活疫苗组为 2 2 % ,而载体和PBS对照组的CTL活性分别为 17%和 18%。一次免疫后 ,实验组小鼠血清结合抗体阳转率为 90 %。除DNA疫苗组外 ,各组小鼠的二次免疫血清抗体效价高于一次免疫的抗体效价 (P <0 0 5 ) ,且以VLPs加佐剂组小鼠血清抗体效价最高 ,Eps加佐剂组次之 ,均高于 pV/JE组和灭活疫苗组 (P <0 0 5 )。三种疫苗可诱发小鼠产生中和抗体。各实验组小鼠能够抵抗JEV的攻击 ,而对照组小鼠的死亡率为 37 5 %。结论　三种新型疫苗可以正确表达JEV的E蛋白表位 ,可诱发免疫小鼠产生抗JEV的中和抗体并有保护性作用 ,免疫效果优于灭活疫苗 ,有可能成为候选的JEV新型疫苗。     

人狂犬病免疫球蛋白联合狂犬病疫苗对暴露后患者伤口愈合的影响

对于犬等动物引起的暴露后三类损伤,依据卫生部<狂犬病暴露后处置工作规范(试行)>,处理原则是在接种狂犬病疫苗的同时应用人狂犬病免疫球蛋白或(马)抗狂犬病血清治疗.人狂犬病免疫球蛋白的主要作用是快速中和狂犬病病毒,防治狂犬病,对伤口抗感染和加快愈合也起促进作用.本研究观察暴露后三类损伤患者在接种狂犬病疫苗的同时,注射人狂犬病免疫球蛋白对伤口的治疗作用.     

Vero细胞在人用狂犬病疫苗中的研究和应用进展

Vero细胞是WHO认可的疫苗生产用细胞,已成为全世界疫苗生产推荐的细胞基质.因其易于生长、可在微载体的发酵罐中大规模扩增、可模式化培养且在限定代次内细胞性状比较稳定的特点,受到疫苗研发与生产工作者的青睐.Vero细胞正式用于人用狂犬病疫苗的生产也有40多年的时间,对狂犬病疫苗的推广使用和狂犬病的预防发挥了重要的作用....     

狂犬病固定毒Vero细胞适应株3aG-V的生物学特性研究

对狂犬病固定毒Vero细胞适应株 3aG V的生物学特性进行了研究 ,包括病毒的形态、抗原结构、培养条件、致病性、免疫原性、纯毒试验及其在中枢神经系统是否形成尼氏小体检查。结果表明狂犬病病毒 3aG V株具有抗原性好 ,培养产毒量高 ,保持有aG固定株弱毒性、传代稳定、无变异 ,可作为替代地鼠肾细胞狂犬病疫苗aG毒株 ,用于Vero细胞培养病毒生产出毒液毒力高 ,灭活后效力高 ,安全性好的纯化Vero细胞狂犬病疫苗的生产用疫苗株。     

Vero细胞口服狂犬病疫苗的研究

本试验采用ＣＴＮ－１株经Ｖｅｒｏ细胞传１５代，病毒滴度均在７．０～８．０ｌｏｇＬＤ５０／ｍｌ之间。给８只犬分别口服８．１ｌｏｇＬＤ５０的疫苗３０天的中和抗体几何平均效价为１：１１０，中和抗体的平均国际单位为２．５９ＩＵ／ｍｌ，阳转率为１００％；给４只犬分别口服７．４３ｌｏｇＬＤ５０的疫苗，阳转率为５０％，中和抗体的平均国际单位为２．４８ＩＵ／ｍｌ。选用３５－６０日龄的乳犬１６只口服１０个剂量的疫苗，并在口服后５、１０、２０天、３个月各杀３只犬取脑及唾液腺分别在ＢＨＫ２１细胞上盲传２代，同时在昆明种小白鼠乳鼠脑内盲传２代，进行病毒分离，均为阴性，余下犬观察１２个月均正常。总之该口服狂犬病疫苗对犬具有较好的安全性及口服免疫原性。     

Anti-rabies antibody titers among subjects who received rabies post-exposure prophylaxis with foreign-made rabies vaccines at the beginning and followed with Japanese rabies vaccine

Recently travelers who were bitten by possibly rabid animals in rabies endemic regions and returned to Japan have increased in number. About half of them received rabies post-exposure prophylaxis (RPEP) with one or more doses of foreign-made rabies vaccines (FRV) in the local medical institutions. FRV, however, are not available in Japan so we have to continue the RPEP with Japanese rabies vaccine (JRV). It has not been demonstrated that an anti-rabies antibody induced with JRV following Vero cell rabies vaccine (PVRV) or chick embryo cell rabies vaccine (PCEC) could be high enough to prevent clinical rabies. We examined anti-rabies antibody (ARA) titers among the subjects visited our vaccine clinic to receive RPEP and obtained results as follows: the ARA titers after a total of 5 doses of PCEC or PVRV and JRV were high enough to prevent clinical rabies as after 5 doses of JRV. However, ARA titers obtained after receiving one dose of PVRV and 2 doses of JRV seemed lower than those produced after one dose of PCEC and 2 doses of JRV or 3 doses of JRV. To accelerate antibody production, consequently, the simultaneous intradermal and subcutaneous injection method of rabies vaccine may be applied to those who were bitten in their hands or head by possibly rabid animals and received only one dose of PVRV in rabies endemic regions.     

Immunogenicity and effectiveness of post-exposure rabies prophylaxis with a new chromatographically purified Vero-cell rabies vaccine (CPRV): a two-stage randomised clinical trial in the Philippines

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (PVRV) (Verorab; Pasteur Merieux Connaught). The immunogenicity and effectiveness of post-exposure rabies prophylaxis with this new vaccine were evaluated in a two-stage clinical trial conducted in the Philippines. In both study stages. post-exposure treatment consisted of five injections of vaccine [(D)ays 0, 3, 7, 14, 28], together with a dose of rabies immunoglobulin (RIG) of equine or human origin on D0. In stage 1, 231 subjects with low-risk rabies exposure (WHO category I or II), and who had a negative ERIG skin test, were treated with either CPRV (n = 114) or PVRV (n = 117). By D14, all subjects in each group had achieved rabies antibody titres over ten times that recommended by the WHO as indicating seroconversion (> or = 0.5 IU/ml). The kinetics of the immune response to vaccination were very similar in the two groups, and at D28, the immunogenicity of CPRV was equivalent to that of PVRV (one-sided equivalence test). Following these positive results, 132 subjects with severe rabies exposure were included in the second stage of this trial. All were scheduled to receive four vaccine doses with CPRV. After D14, only those 57 patients with confirmed rabies exposure (animal with positive FA test) and seven patients for whom rabies exposure could not be excluded (animal lost or not tested) completed the treatment and were followed for one year to assess survival. After 1 year, 62 patients treated for confirmed or possible severe rabies exposure had been examined and were still alive. Two patients contacted by letter and telephone confirmed good health 7 and 16 months after exposure. No severe local or systemic reactions were reported in either stage of the study, and no treatment-related serious adverse event occurred. This two-stage clinical trial attests to the safety and satisfactory immunogenicity of CPRV in post-exposure rabies treatment, and confirms the effectiveness of a new rabies vaccine in patients with severe confirmed exposure.     

Simulated post-exposure rabies vaccination with purified chick embryo cell vaccine using a modified Thai Red Cross regimen.

OBJECTIVES: Currently, two intradermal regimens for the administration of cell culture rabies vaccines are approved by the WHO for rabies post-exposure prophylaxis: the two site Thai Red Cross regimen (TRC) and the eight site regimen. For the TRC regimen the volume of vaccine recommended per dose is 0.1 ml of purified Vero cell rabies vaccine (PVRV) and 0.2 ml of purified chick embryo cell vaccine (PCEC). The objective of the present study was to evaluate comparatively the immune response to PCEC and PVRV vaccines administered by the TRC regimen using a uniform dose of 0.1 ml of vaccine. METHODS: Forty-two subjects received TRC regimen (2-2-2-0-1-1) with 0.1 ml of PCEC vaccine and 38 subjects received the same regimen with PVRV. The rabies neutralizing antibody response in these subjects on days 10, 28, 90 and 180 was determined by the standard mouse neutralization test (MNT). RESULTS: There was adequate antibody response with both the vaccines and 100% seroconversion was observed by day 10. Furthermore, the antibody titers obtained with PCEC did not differ significantly from those obtained with PVRV on all days tested (p > 0.05). CONCLUSIONS: It can be concluded from the results that an adequate antibody response can be obtained with PCEC vaccine when administered by the TRC regimen even after reducing the quantity of vaccine from 0.2 ml to 0.1 ml per intradermal dose. The feasibility of using this regimen in true post-exposure cases needs to be further evaluated.     

Failure of pre- and postexposure rabies vaccinations in a child infected with HIV.

We report the case of a 6-y-old HIV-infected girl with severe immune deficiency who failed to respond to intramuscular pre-exposure rabies vaccination using human diploid cell rabies vaccine on days 0, 7 and 28. She also failed to respond to an intradermal postexposure rabies regimen using purified verocell rabies vaccine at 4 sites on days 0, 3 and 7 and at 2 sites on days 30 and 90 (double the usual regimen). Sequentially monitored rabies neutralizing antibody titers were below the WHO minimum acceptable level (> 0.15 IU/ml) in all specimens. Rabies prevention in HIV-infected persons with severe immune suppression requires further study.     

Early antibody responses to rabies post-exposure vaccine regimens

The aim of post-exposure rabies vaccine treatment is to induce immunity, measured as neutralizing antibody, as fast as possible. This is especially important in the tropical rabies-endemic areas where simultaneous passive prophylaxis with hyperimmune serum is not practicable in the majority of cases. We compared the rate of production of antibody during the first two weeks, by six vaccine regimens in 118 subjects using two tissue culture vaccines, human diploid cell strain vaccine (HDCSV) and purified Vero cell rabies vaccine (PVRV). No antibody was detected on day 5. On day 7, the highest seroconversion rate was seen in subjects given HDCSV intramuscularly at two sites on days 0 and 3 (7 of 15), but this was not significantly different from the group with the lowest rate: the conventional single-site intramuscular regimen. All subjects had antibody by day 14, at which time the highest geometric mean titer was in the group vaccinated with 0.25 ml doses of diploid cell vaccine given subcutaneously at eight sites. This regimen, together with the standard single-site diploid cell vaccine and an eight-site intradermal regimen of the same product gave significantly higher titers than the two-site intramuscular regimens of either product. No single immunization schedule emerges as best, so the speed of antibody response, economy, and the skill needed for intradermal injection should be considered when deciding on the optimum regimen for use in a particular geographic area.     

Preventing rabies with the Verorab vaccine: 1985-2005 Twenty years of clinical experience

Purified rabies vaccine cultured on Vero cells (Verorab, sanofi pasteur) is WHO-approved for pre- and post-exposure prophylaxis by intradermal and intramuscular routes. During 20 years of use, over 40 million doses of Verorab have been administered in more than 100 countries. No serious adverse event due to Verorab has been reported in clinical trials involving 3937 persons, and Verorab is better tolerated than human diploid cell vaccine (HDCV). Pre-exposure prophylaxis is confirmed immunogenic in 1437 subjects by all routes, with prompt responses following boosting; Verorab boosts effectively subjects pre-immunized with HDCV. Unlike HDCV, Verorab is not associated with post-boosting serum sickness. In the absence of data in immunodeficient/HIV-positive individuals, pre-exposure immunization is urged as early as possible. Essen, Zagreb, Thai Red Cross Intradermal (TRC-ID) and other post-exposure intramuscular and intradermal regimens are documented. Two thousand one hundred and eighty-three subjects received post-exposure prophylaxis, including 874 high risk, severe or confirmed rabid attacks. Co-administration of rabies immune globulin (RIG) does not affect neutralizing antibody levels when Essen or TRC-ID regimens are employed; levels are lower with the Zagreb regimen. Verorab has been administered safely and effectively post-exposure to 251 pregnant women, without any increase in congenital malformations or spontaneous abortions. From a pediatric perspective, safety and efficacy have been demonstrated in 759 children (0-15 years). Intradermal post-exposure Verorab is an effective and inexpensive option for developing countries. Inadvertent subcutaneous administration does not reduce immunogenicity. WHO already strongly recommends the replacement of nerve tissue vaccines with modern vaccines. Extensive clinical experience supports the use of Verorab for intramuscular and intradermal pre- and post-exposure prophylaxis, including in special situations.     

Rabies vaccine prepared in human cell cultures: progress and perspectives

Rabies vaccine prepared in human diploid cell strains is a replacement for the previously available vaccines that are prepared in animal tissues and are less immunogenic and more reactogenic. The human cel-grown vaccine made in the United States is a split-product vaccine, whereas the vaccines made in Europe are whole-virion vaccines. Both types of vaccine contain concentrated and inactivated "fixed" rabies virus. When used before exposure to rabies virus, the vaccine should be given intramuscularly in three 1-ml doses on days 0, 7, and 21. Immediately after exposure to rabies virus, a person should be given human rabies immune globulin (20 international units/kg). This treatment should be followed by five intramuscular doses of vaccine given on days 0, 3, 7, 14, and 28. For maintenance of long-term immunity in persons continously exposed to the risk of rabies, booster doses of the vaccine should be given at two-year intervals.