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.     

Survival of neutralizing antibody in previously rabies vaccinated subjects: a prospective study showing long lasting immunity

Physicians dealing with potential rabies exposures and travel medicine are frequently asked how long previous pre- or post-exposure rabies vaccination induced immunity persists. We therefore carried out a prospective study on 118 rabies vaccine recipients who had received pre- or post-exposure regimens with tissue culture rabies vaccines by intramuscular or intradermal schedules 5-21 years previously. Rabies neutralizing antibody was detectable in the sera of all subjects on day 0. They then received one intradermal 0.1 mL booster injection on days 0 and 3. Neutralizing antibody determination was carried out on days 5, 7 and 14. All except one subject showed an accelerated antibody response following the two booster injections. Vaccination with a WHO recognized tissue culture rabies vaccine evokes long lasting immunity. This study supports current recommendations that immunity is long lasting and that boosters without immunoglobulin are sufficient even when prior vaccination was longer than 5 years previously.     

Potency,sterility and immunogenicity of rabies tissue culture vaccine after reconstitution and refrigerated storage for 1 week

The economical Thai Red Cross intradermal (TRC-ID) post-exposure rabies treatment schedule is now widely used in Asia. However, directives from WHO and manufacturers mandated that the vaccine be used within 8h after reconstitution of the freeze-dried product. This limits the use of TRC-ID to large animal bite clinics that see several rabies exposed patients daily. This study demonstrated that refrigerated purified chick embryo and Vero cell rabies vaccines can be stored safely for up to 7 days after reconstitution; allowing use of this treatment regimen in clinics that see few rabies exposed subjects. A large project applying this method in a Northern Thai canine rabies endemic province is now in place.     

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.     

Immunogenicity, safety and lot consistency in adults of a chromatographically purified Vero-cell rabies vaccine: a randomized, double-blind trial with human diploid cell rabies vaccine

The immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) was evaluated using US veterinary medical students. In the first study, 242 healthy adults were enrolled in a randomized, modified double-blind, multicenter trial and received five doses of either CPRV or human diploid cell vaccine (HDCV) by intramuscular injection on days 0, 3, 7, 14, and 28 concurrently with human rabies immunoglobulin in a simulated post-exposure prophylaxis regimen. Post-immunization titers in the CPRV and HDCV groups reached 0.5 IU/ml (the WHO-recommended minimally acceptable titer) or greater in all subjects in both vaccine groups by day 14 and remained above that level through day 90. In the second study, 438 healthy adults were enrolled in a randomized, double-blind, multicenter trial and assigned to receive five doses from one of three lots of CPRV by intramuscular injection on days 0, 3, 7, 14, and 28 in a simulated post-exposure prophylaxis regimen to evaluate lot consistency. Post-immunization titers rapidly increased to over 0.5 IU/ml by day 14 for all subjects and remained above that level through day 42 when the study was terminated. The three lots were considered equivalent. The percentage of subjects with at least one local reaction during the five-dose regimen was slightly lower in the CPRV group than in the HDCV group (P=0.06). The most frequently reported local reaction for all doses of vaccine was pain at the injection site. Headache, myalgia, and malaise were the most frequently reported systemic events. The percentage of subjects with at least one systemic event was significantly lower for CPRV (P=0.0084). No vaccine-related serious adverse reaction was reported in these studies. The results of these studies indicate that CPRV administered intramuscularly to healthy adults is immunogenic and is associated with fewer local and systemic reactions than HDCV.     

Rabies intradermal post-exposure vaccination of humans using reconstituted and stored vaccine

Thailand's northern Petchabun province is endemic for canine rabies. There were 27 reported human rabies deaths between 1989 and 1998. A rabies control plan was formulated in 1997 between medical and veterinary public health officials. It started an intense education program and an ongoing dog vaccination campaign. Economic constraints and the high cost of biological were the main reasons for inadequate human post-exposure management (PET). It was therefore decided to use the economical Thai Red Cross Intradermal Vaccine Regimen (TRC-ID) throughout the province. The original TRC-ID method is only suitable for clinics that see more than one PET patient daily. TRC-ID was therefore modified by storing the reconstituted vaccine in a refrigerator for the same patient's next two visits. Data on a total of 8157 PET patients were collected. An additional modification of TRC-ID also eliminated the 90 day booster. There were no treatment failures and no human rabies deaths in 1999, 2000 and 2001. The modified TRC-ID method induces adequate levels of neutralizing antibodies, protects humans bitten by rabid dogs and results in significant savings in vaccine and travel costs.     

Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: A randomised phase II pre-exposure prophylaxis study

A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a satisfactory safety profile and was immunogenically non-inferior to the licensed purified Vero cell rabies vaccine in adults. Here, we evaluated the safety and immunogenic non-inferiority of PrEP with PVRV-NG compared to the licensed human diploid cell vaccine (HDCV) in healthy adults (NCT01784874). Participants received three vaccinations (days 0, 7, and 28) as PrEP with or without a booster injection after 12 months. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 28 (subgroup only), and 42, and Months 6, 12, and 12 + 14 days (booster group only). Non-inferiority (first primary objective) was based on the proportion of participants with RVNA titres ≥ 0.5 IU/mL (World Health Organization criteria for seroconversion) on day 42, expected to be ≥ 99% (second primary objective). Safety was evaluated after each dose and monitored throughout the study. At day 42, PVRV-NG was non-inferior to HDCV and the first primary objective was met; seroconversion was observed for 98.3% of PVRV-NG recipients and 99.1% of HDCV recipients. As < 99% of participants in the PVRV-NG group had RVNA titres ≥ 0.5 IU/mL, the second primary objective was not met. Booster vaccination produced a strong increase in RVNA titres for all groups, primed with PVRV-NG or HDCV. RVNA geometric mean titres tended to be higher for HDCV than PVRV-NG primary vaccine recipients. In a complementary evaluation using alternative criteria for seroconversion (complete virus neutralization at 1:5 serum dilution), 99.6% and 100% of participants in the PVRV-NG and HDCV groups, respectively, achieved seroconversion across the vaccine groups. No major safety concerns were observed during the study. PVRV-NG was well tolerated, with a similar safety profile to HDCV in terms of incidence, duration, and severity of adverse events after primary and booster vaccinations.ClinicalTrials.gov number: NCT01784874.     

Human diploid cell rabies vaccine purified by zonal centrifugation: a controlled study of antibody response and side effects following primary and booster pre-exposure immunizations

Systemic allergic reactions following booster immunizations have complicated rabies pre-exposure prophylaxis with the human diploid cell rabies vaccine licensed in the US (conventional HDCV). We conducted two studies comparing an HDCV purified by zonal centrifugation to conventional HDCV. In a study of primary pre-exposure immunization, volunteers received one of four regimens: three 1.0-ml intramuscular (i.m.) or 0.1-ml intradermal (i.d.) doses of conventional or purified HDCV over 28 days. Although volunteers vaccinated i.m. had significantly greater rabies neutralizing antibody titres (VNA) 49 days, 91 days and 26 months after immunization began than volunteers vaccinated i.d. (p less than 0.005-p less than 0.05), there were no significant differences between vaccines. In a study of booster immunizations, 77 volunteers immunized with conventional HDCV 2 years earlier received a 0.1-ml i.d. booster with either conventional or purified HDCV. VNA was significantly greater with the conventional HDCV on days 7 and 28 after booster, but not on day 365. A moderate or severe reaction was reported by 5 (13%) of the 40 persons who received boosters with conventional HDCV, versus none of 37 who received the purified HDCV (p = 0.03). Purified HDCV appears to be preferable to conventional HDCV for booster vaccination.     

Reduced dose pre-exposure primary and booster intradermal rabies vaccination with a purified chick embryo cell vaccine (PCECV) is immunogenic and safe in adults

Pre-exposure vaccination of persons at risk with intradermally administered reduced dose cell culture rabies vaccines remains controversial in low-enzootic countries. In a prospective clinical trial of adult volunteers (N=25), we studied the immune response to purified chick embryo cell vaccine (PCECV) administered intradermally at a reduced dose (0.1 mL) in a three-dose schedule (0, 7 and 21 days). In 10 subjects, immunogenicity of intradermally administered one-dose booster vaccination with 0.1 mL PCECV was investigated. All participants were seroconverted 3 weeks after primary and 1 week after booster vaccination (antibody titre > or = 0.5 EU/mL, measured by enzyme linked immunosorbent assay). Local adverse events such as erythema and swelling were moderate and transitory. The intradermal vaccination route offers an efficacious and cost-reducing strategy to increase the accessibility of cell culture rabies vaccines.     

Intradermal immunization with human diploid cell rabies vaccine: serological and clinical responses of immunized persons to intradermal booster vaccination.

Rabies antibody titers ranged from 0-9.3 IU/mL in 117 human volunteers one year after intradermal vaccination with one or two doses of human diploid cell rabies vaccine (HDCV). At that time, each volunteer received one 0.1-mL booster dose of HDCV intradermally. All 117 volunteers showed good anamnestic responses, with antibody titers rising to 0.5-54.3 IU/mL within seven days of booster injection. Vaccine safety was good; only minor reactions were experienced, all of which resolved spontaneously.     

Effectiveness and tolerance of pre- and postexposure treatment with purified inactivated rabies vaccine prepared on Vero cell line

The results are reported of a field trial which was designated to demonstrate the inocuity and efficacy of the purified inactivated rabies vaccine (PVRV), produced on Vero cells by the Institut Mérieux, Lyon, France in pre- and postexposure treatment in man. Four sex and age matched groups of veterinary students and medical personnel received the vaccine. The vaccine was given according to WHO recommendations for pre- and postexposure regimens. The 82 volunteers were divided into four groups and vaccinated as follows. Group IA consisted of 27 individuals, receiving injections on days 0, 7 and 21. Group IB consisted of 29 individuals, injected on days 0, 28 and 56. Group II consisted of 16 individuals, receiving a postexposure schedule of vaccinations on days 0, 3, 7, 14, 28 and 90. Group III consisted of 10 subjects, all of whom had been previously immunized with various antirabies vaccines and received one single booster inoculation of this vaccine. Serum samples were taken on the days of vaccination and 14 days later in all groups and in addition on day 70 in group IA. Neutralizing antibodies against the rabies virus were determined in the rapid fluorescent focus inhibition test (RFFIT). In conclusion it can be stated that, regardless of the schedule of prophylactic immunization, three 0.5 ml inoculations of PVRV result in very high titres of virus neutralizing antibodies and a single vaccination in previously immunized individuals is sufficient to raise the amount of antibodies to a high level. Due to the high purity of the product the vaccine is very well tolerated by the vaccinees.     

An immunogenicity study of a newly introduced purified Vero cell rabies vaccine (Abhayrab) manufactured in India

Purified Vero cell culture rabies vaccine "Abhayrab" manufactured by Human Biologicals Institute, Ooty, India was subjected for immunogenicity studies. Pre-exposure study was undertaken on 60 healthy volunteers (Group I) with vaccination on days 0, 7 and 21. A group of 75 patients of category II (Group II), 67 of category III (Group III) were given post-exposure prophylaxis and 88 patients of category III were administered with rabies immunoglobulins (Group IV) along with post-exposure prophylaxis as per World Health Organization (WHO) recommendations with a booster on day 90. The volunteers and patients vaccinated showed very few adverse side effects. The blood samples collected from volunteers (Group I) on days 14, 35 and 365 and patients (Group II-IV) on days 14, 30, 90 and 365 showed geometric mean titres (GMT) of >0.5 IU/ml. The study indicated new rabies vaccine manufactured in India was found to be safe and immunogenic.     

One-year study of the 2-1-1 intramuscular postexposure rabies vaccine regimen in 100 severely exposed Thai patients using rabies immune globulin and Vero cell rabies vaccine.

The 2-1-1 rabies postexposure treatment schedule is an abbreviated regimen in which a tissue culture rabies vaccine is administered intramuscularly at two sites on day 0, and at one site on days 7 and 21. Compared to the standard five-dose intramuscular regimen, the 2-1-1 schedule reduces the number of clinic visits from five to three and the amount of vaccine used by 20%. One hundred Thai patients, who were severely exposed to rabies, were treated with rabies immune globulin and the 2-1-1 regimen using purified Vero cell rabies vaccine. They were followed for 1 year. Rabies antibody titres were measured in 10% of this group. All patients survived and adverse reactions were mild. A satisfactory antibody response (a titre greater than 0.5 IU ml-1) occurred in all ten patients studied at day 14, but persisted for 90 days in 80% and for 360 days in only 50%. The authors therefore do not recommend use of the 2-1-1 schedule in severely exposed patients who also need to receive rabies immune globulin.     

A serum-free,purified vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab™ for pre-exposure use in healthy adults: Results from a randomized controlled phase-II trial

Background

Verorab™ was licensed in 1985 for both pre- and post-exposure prophylaxis of rabies. The next generation purified Vero cell rabies vaccine (PVRV-NG) is a highly purified vaccine. We performed a phase II clinical study in adults in France to assess its immunological non-inferiority and clinical safety for pre-exposure prophylaxis.

Methods

In a randomized phase-II trial, 384 healthy adult subjects were randomized (2:1) to receive a three-dose primary series of PVRV-NG or Verorab. One year later, the PVRV-NG group received a PVRV-NG booster while the Verorab group participants were randomized to receive a booster of PVRV-NG or Verorab for. Rabies virus neutralizing antibodies (RVNA) were evaluated on days 0, 28 (subgroup), 42, months 6, 12 and 12 + 14 days. Safety was evaluated for seven days after each dose. Adverse event between doses, until 28 days after the final dose was recorded. Serious adverse events were recorded up to 6 months after the last dose.

Results

The criterion for non-inferiority was met in the per-protocol analysis set and confirmed in the full analysis set (FAS). In the FAS, 99.6% and 100% of subjects had RVNA titers ≥0.5 IU/mL in PVRV-NG and Verorab groups, respectively. While RVNA levels gradually decreased over the 12-month period, at 6 and 12 months after vaccination >89% and >77%, respectively, in both groups had RVNA titers ≥0.5 IU/mL. The PVRV-NG booster induced a strong response, irrespective of the vaccine given for the primary series. PVRV-NG was safe and well tolerated and its safety profile was similar to Verorab for unsolicited adverse events and solicited systemic reactions. The incidence of solicited injection-site reactions was lower with PVRV-NG than with Verorab after the primary series and the booster dose.

Conclusions

PVRV-NG was shown to be at least as immunogenic as Verorab and to present a similar safety profile.     

Rabies neutralizing antibody after 2 intradermal doses on days 0 and 21 for pre-exposure prophylaxis

Pre-exposure prophylaxis is recommended for people who will be exposed to rabies virus in the laboratory or who will contact with mammals. World Health Organization recommends 2 doses of a cell-culture rabies vaccine given 1 week apart, and a third booster dose given 2–3 weeks later. Neutralizing antibody response is virtually 100%, and the individual remains sensitized indefinitely. Intradermal pre-exposure regimen for rabies prophylaxis is more economical compared with the conventional intramuscular regimen in terms of vaccine volume. However, both regimens require three clinic visits. In order to reduce non-medical expenses such as transportation to the clinics and to increase compliance, the immunogenicity and safety of two-visit intradermal regimen for pre-exposure prophylaxis were studied. Fifty-five healthy subjects aged between 18 and 24 years were enrolled and divided into two groups. Group A (n = 39) received 0.1 ml of purified Vero cell rabies vaccine (PVRV; Sanofi Pasteur, Lyon, France; Lot no. Z0996 with an antigenic value of 4.8 IU/0.5 ml vial) intradermally each at two sites on days 0 and 21. Group B (n = 16) received 0.5 ml of PVRV intramuscularly on days 0, 7 and 21, as conventional intramuscular regimen for pre-exposure prophylaxis. Rabies neutralizing antibody (Nab) titers were measured on days 0, 35, 365 and 379 (14 days after simulated post-exposure booster vaccination). All subjects from two groups had Nab titers ≥0.5 IU/ml on day 35. In addition, the difference between geometric mean titers for group A (4.51 IU/ml; range of Nab titers 1.69–13.0 IU/ml) and group B (6.74 IU/ml; range of Nab titers 2.20–14.23 IU/ml) on day 35 was not statistically significant (p > 0.05). One year after pre-exposure vaccination, all subjects in both groups received simulated post-exposure booster vaccination with 0.1 ml of PVRV ID on days 0 and 3 (day 365 and day 368 after pre-exposure vaccination). After simulated booster vaccinations with 0.1 ml PVRV ID on days 0 and 3, all subjects in groups A (GMT 14.38 IU/ml; range 2.99–308.44 IU/ml) and in group B (GMT 14.06 IU/ml; range 3.12–62.09 IU/ml) had rabies Nab titers ≥0.5 IU/ml on day 14 post-booster (p > 0.05). Mild local adverse events such as pain at injection site, pruritus and erythema were observed. Our study indicated that 2-site intradermal pre-exposure regimen on days 0 and 21 with 0.1 ml of cell-culture rabies vaccine is safe and immunogenic as the conventional intramuscular regimen.     

A randomized open-label trial of 2-dose or 3-dose pre-exposure rabies prophylaxis among Thai children

BackgroundWorld Health Organization changed the recommendation for pre-exposure rabies prophylaxis from 3-dose to 2-dose regimen in 2018. Given limited data of 2-dose regimens in pediatric population, this study aimed to compare the immunogenicity between 2-dose and 3-dose pre-exposure rabies immunization.MethodsThis study was conducted among healthy children aged 2–12 years. They were randomized to 2-dose vaccination (2D) on days 0 and 28 or 3-dose vaccination (3D) on days 0, 7, and 28. Purified Vero cell rabies vaccine (PVRV-Verorab™) was administered intramuscularly. Rabies virus neutralizing antibody (RVNA) titers were measured at 3 time points: 14-day after complete vaccination, 1-year pre-booster vaccination, and 7-day post-booster dose to mimic scenario of rabies exposure. RVNA titers ≥0.5 IU/ml were considered adequate antibody. T cell specific response to rabies vaccine antigen was measured using the interferon-gamma enzyme linked immunospot assay.ResultsFrom September to October 2017, 107 participants (51% males), 78 in 2D group and 29 in 3D group were enrolled. Median age was 5.8 years (IQR 4.4–7.3). All participants had RVNA titers ≥0.5 IU/ml after primary vaccination [GMT 2D: 18.6 (95%CI 15.9–21.8) and 3D: 16.3 (95%CI 13.2–20.1 IU/ml), p = 0.35]. At 1-year prior to receiving the booster, only 80% of the children in 2D group maintained RVNA titers ≥0.5 IU/ml compared to 100% of the children in 3D group (p = 0.01). However, all participants in both groups had RVNA ≥0.5 IU/ml at 7-day post booster vaccination [GMT 2D: 20.9 (95%CI 17.4–25.3) and 3D: 22.2 (95%CI 15.8–31.4) IU/ml (P = 0.75)]. The median number of IFN-γ secreting cells at 7-day post-booster dose was 98 and 128 SFCs per 10⁶ PBMCs in the 2D and 3D groups, respectively (P = 0.30).ConclusionsTwo-dose primary rabies immunization provided adequate antibody at post primary vaccination and post booster. The results support 2-dose regimen of pre-exposure rabies immunization in the pediatric population.     

人用Vero细胞狂犬病疫苗暴露前免疫的安全性和免疫效果观察

目的为观察人用Vero细胞狂犬病疫苗暴露前免疫程序的安全性和效果。方法征集志愿者65人,暴露前接种3剂人用Vero细胞狂犬病疫苗,分别于第0d、7d、28d肌内注射。次年第1针免疫后的第365d加强1剂。用小鼠脑内中和试验测定其抗狂犬病病毒抗体。结果所有志愿者均未出现局部反应、全身反应和严重不良反应。65名志愿者在第1次接种前,除1名血清抗体为0.5IU/ml外,其余均未测出抗体。第45d、365d、385d的血清抗体阳转率分别为100.00%、90.57%、100.00%,几何平均滴度分别为12.82IU/ml、1.57IU/ml、40.49IU/ml。结论人用Vero细胞狂犬病疫苗在暴露前免疫程序安全且效果好。     

An evaluation of second generation tissue culture rabies vaccines for use in man: a four-vaccine comparative immunogenicity study using a pre-exposure vaccination schedule and an abbreviated 2-1-1 postexposure schedule

In a double-blind comparative trial the immunogenicity of three new tissue culture rabies vaccines was evaluated, using a commercial human diploid cell vaccine (HDCV) lot as the reference. Two different vaccination regimens, a pre-exposure schedule, and an abbreviated 2-1-1 postexposure schedule (two doses of the vaccine applied bilaterally on day 0, with subsequent single doses given on days 7 and 21) were employed. In both, two of the new vaccines, purified chick embryo cell vaccine and purified Vero rabies vaccine, induced an antibody response equivalent to that of HDCV, while the geometric mean titres for the fetal bovine kidney cell vaccine were somewhat lower. The 2-1-1 regimen, a candidate regimen for economical rabies postexposure treatment, evoked a rapid and high titre antibody response with all four vaccines, peaking on day 14.     

Immunogenicity and safety of a new Vero cell rabies vaccine produced using serum-free medium

The immunogenicity and safety of a new human rabies vaccine, produced in Vero cells by a process that does not require supplementation with human or animal derived components in production, were assessed. Thus, the objective is to produce a safer vaccine at a lower cost. A total of 296 volunteers was divided into two groups: Group 1, which received the study vaccine, and Group 2, which received the Vero cells vaccine produced by Sanofi Pasteur. Five doses were given on days 0, 3, 7, 14 and 28. Blood samples for determination of rabies virus neutralizing antibodies were collected on days 0, 14, 38 and 90. The geometric mean titers (GMT) were much higher than 0.5 IU/ml in both groups on days 14, 38 and 90, indicating seroconversion according to the World Health Organization. In Group 1, however, the GMTs were higher than in Group 2, the difference being statistically significant in the two last samples. There was no statistical difference between the groups in the ratio of individuals with titers > or =0.5 IU/ml in each sample. Pain at the injection site was the most common adverse reaction and occurred most often in Group 1 (p < 0.001). All cases had a favorable evolution. There were no severe adverse reactions. It was concluded that the new vaccine is safe and immunogenic.     

液体与冻干狂犬病疫苗临床反应与免疫原性观察

目的研究液体与冻干狂犬病疫苗的临床反应和免疫原性。方法对300例暴露于狂犬病的病人进行常规5针注射,其中100例使用国产Vero细胞液体狂犬病疫苗,100例用国产Vero细胞冻干狂犬病疫苗,100例用进口Vero细胞冻干狂犬病疫苗,观察每针注射后的局部反应和全身反应;在免疫后14d和42d(全程注射后14d)用间接免疫荧光法检测抗体水平。结果国产液体疫苗、国产冻干疫苗和进口冻干疫苗局部反应发生率分别是28.6%、3.6%、3.2%。全身反应发生率分别是4.4%、1.2%、0.8%。免疫14d后国产液体疫苗、国产冻干疫苗、进口冻干疫苗的抗体阳转率分别是82%、96%,98%。免疫42d后抗体阳转率分别93.68%、98.98%、98.99%。结论冻干狂犬病疫苗的临床反应和免疫原性优于液体狂犬病疫苗。