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.     

Immunogenicity of purified chick embryo cell anti-rabies vaccine in post-exposure treatment of animal bite cases

The observations on immunogenicity of Purified Chick Embryo Cell (PCEC) anti rabies vaccination in post-exposure prophylaxis is reported. In total 207 serum samples collected from patients receiving 3 to 6 doses of PCEC were analysed for the presence of anti-rabies antibodies. The samples were collected from 10 days to 11 months after the last dose of vaccine. All the vaccinees (n=33) tested after 3 doses of PCEC showed protective titres (> or = 0.5 IU/ml) and those receiving 5-6 doses (n=161) showed 4-5 times higher than protective titres. The analysis pertains to specimens collected at one point of time only after the vaccination. However, in all 17 vaccinees where samples were collected 7-11 months after 3-6 doses of vaccine, the protective titres were sustained, these being 3-4 times higher than the protective titres in those receiving 5-6 vaccine doses. The results indicated that there was no need of routine anti-rabies antibody monitoring in healthy individuals receiving post-exposure prophylaxis in recommended doses of vaccine.     

A case received pre-exposure immunization against rabies by intradermal injection of rabies vaccine because of allergic reaction to the component of the vaccine]

A female, 25 years of age, came to our clinic to receive pre-exposure immunization against rabies. In another hospital she was tested to find out whether she was allergic to the components of rabies vaccine (PCEC) manufactured by the Chemo-Sero-Theraptic Research Institute (Kaketsuken) by cutaneous reaction using a 2,000-fold diluted PCEC. She showed a positive reaction. In our clinic she was again examined by skin test using 0.1 ml of 10-fold diluted PCEC. She showed wheal and flare reaction. Further we tested using 0.05 ml and 0.1 ml of non-diluted PCEC. Her skin reaction did not increase by several mm in diameter. So we decided to immunized her against rabies with intradermal injections of PCEC instead of subcutaneous injections that is indicated by the manufacturer. The second intradermal injections were done to right and left forearms a week later. Then the third shot was given 4 weeks after the second. At 2 weeks after the third injection her blood sample was taken to measure anti-rabies antibody titer by ELISA method with Platelia rabies kit (Diagnostic Pasteur, France). She had 6.7 U/ml of anti-rabies ELISA antibody that was much higher than the protective level (0.5 IU/ml) officially recognized by WHO. Therefore, it is concluded that she had produced sufficiently high level of anti-rabies antibody with intradermal injection of PCEC. It is reasonably recommended to investigate further if the intradermal injection of PCEC will be an effective method as a pre-exposure immunization against rabies.     

Economical multi-site intradermal regimen with purified chick embryo cell vaccine (Rabipur) prevents rabies in people bitten by confirmed rabid animals.

OBJECTIVE: To determine the efficacy of a cost-effective multi-site intradermal regimen with purified chick embryo cell vaccine (PCECV, Rabipur) in preventing rabies in people bitten by confirmed rabid dogs. METHODS: Thirty-two people of different age groups who were severely bitten by confirmed rabid dogs were immunized with PCECV using the WHO recommended multi-site intradermal regimen of 0.1 mL of vaccine at eight sites on day 0, at four sites on day 7, and at one site each on days 28 and 90. In addition, passive immunization with human or equine rabies immunoglobulin was administered to 22 of these people before administering vaccine. They were followed for up to 3 years with periodic estimation of neutralizing antibody levels in their serum by mouse neutralization test (MNT). RESULTS: There was an excellent immune response with more than protective titers (>0.5 IU/mL) on all days tested up to the end of the 3-year observation period. More significantly, protective titers were seen in all subjects by day 7. Only minimal side effects were observed. All the patients were doing well at the end of the 3-year observation period, which is generally considered to be the maximum incubation period for rabies in humans. CONCLUSIONS: It can be concluded that this multi-site regimen with or without passive immunization has prevented the development of rabies encephalitis in these people bitten by confirmed rabid dogs. This should encourage more such studies, so that this cost-effective economical regimen with safe and potent cell culture vaccines can replace highly reactogenic neural tissue-derived Semple vaccine in developing countries such as India.     

Immune response after rabies vaccine in a kidney transplant recipient

A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented.     

WHO recommended pre-exposure prophylaxis for rabies using Japanese rabies vaccine

After severe exposure to suspected rabid animal, WHO recommends a complete vaccine series using a potent effective vaccine that meets WHO criteria, and administration of rabies immunoglobulin (RIG). RIG is not available globally, and is not marketed in Japan. If pre-exposure prophylaxis for rabies is given, RIG is unnecessary even after severe exposure. It is thus important to give pre-exposure prophylaxis for rabies to people who plan to go to rabies-endemic areas. In Japan, pre-exposure prophylaxis for rabies consists of 3 doses of cell-culture rabies vaccine. The first two doses are given 4 weeks apart, and the third dose is given 6-12 months after the first dose, all of which are injected subcutaneously (standard regimen). People who plan to travel abroad to rabies-endemic areas may know of their destinations only 1 or 2 months in advance at best. Therefore, it is virtually impossible to complete the 3 dose regimen for rabies in Japan. Pre-exposure prophylaxis recommended by WHO consists of 3 doses given intramuscularly on days 0, 7, and 28, making it possible to complete pre-exposure prophylaxis in one month. This WHO recommended pre-exposure prophylaxis using Japanese cell-cultured rabies vaccine (PCEC-K) has not been studied, so we elected to fill the gap using PCEC-K, administered based on the WHO recommendation and examined its efficacy and safety. Subjects were 26 healthy volunteers with no previous rabies vaccination giving oral and written consent. Vaccine was administered on days 0, 7, and 28, and rabies antibody levels were tested on days 7, 28, and 42. On day 7, every antibody level was negative. On day 28, antibody levels were between 0.7-3.5 EU/ mL, with the exception of 3 cases still negative. On day 42, all cases, including the 3 negative cases, exceeded 1.6 EU/mL, providing sufficient protection against rabies. This result was not inferior compared to the standard regimen. Local adverse effects such as erythema and pain were noted, but none were serious. In conclusion, WHO recommended pre-exposure prophylaxis for rabies using PCEC-K is considered effective and safe.     

Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new, highly purified, heat-treated equine rabies immunoglobulin, administered either alone or in association with a purified, Vero-cell rabies vaccine

A clinical evaluation of a new, purified, heat-treated equine rabies immunoglobulin (PHT-Erig), F(ab′)₂ preparation, was carried out in Thailand and in the Philippines—two countries where rabies is endemic. An initial prospective, randomised, controlled trial (Study 1), compared the safety and pharmacokinetics (serum concentrations of rabies antibodies) after administration either of PHT-Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A second trial (Study 2) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV), administered in association with either Erig PMC or PHT-Erig. In Study 1, 27 healthy, Thai adults received a 40 IU kg⁻¹ dose of either Erig PMC (n=12) or PHT-Erig (n=15) via the intramuscular (IM) route; half of the dose was injected into the deltoid area and the other half into the buttocks. Serum for rabies antibody determination and F(ab′)₂ concentration was collected at hours (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were safe, with no serious adverse events, and in particular, no anaphylactic reactions or serum sickness was reported. A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products. Nonetheless, the relative bioavaibility of 93% and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar. The antibody level in either group were low throughout the 15-day study period. The geometric mean titer (GMT) values ranged from group 0.027–0.117 IU ml⁻¹ in the Erig group and from 0.029 to 0.072 IU ml⁻¹ in the PHT-Erig. There was no significant difference between the evolution of GMT values for the two groups. In Study 2, 71 healthy volunteers received 40 IU kg⁻¹ via the intramuscular route of either Erig PMC (n=36) or PHT-Erig (n=35) on D0, in association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and D28. No serious reactions were reported in either group. In particular, no immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were observed. Over the 28-day follow-up period, GMT profiles of the two groups were statistically equivalent. On D14, 100% of the subjects had protective antibody titers (anti-rabies antibodies ≥0.5 IU ml⁻¹, which is the WHO-recommended level of seroconversion), and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen. On D28, the GMT values were 33.2 IU ml⁻¹ (95% CI, 23.8–46.1 IU ml⁻¹) in the Erig PMC/PVRV group and 31.4 IU ml⁻¹ (95% confidence interval, CI, 23.4–42.2 IU ml⁻¹) in the PHT-Erig/PVRV group, showing evidence of adequate vaccine-induced antibody responses in both groups. The increased purity, the heat-treatment step introduced in the manufacturing process of PHT-Erig, and the good clinical results substantiate the use of this new generation, purified equine F(ab′)₂ preparation in the post-exposure prophylaxis of rabies.     

Clinical trials in healthy volunteers with the new purified chick embryo cell rabies vaccine for man

Behringwerke has developed the new, safe and economical purified chick embryo cell (PCEC) rabies vaccine. Due to the purification by zonal centrifugation the compatibility of this vaccine is excellent. Among 933 vaccinations in 219 healthy volunteers the only side-effect was mild pain at the injection-site in 17 vaccinations (1.7 per cent). The sero-conversion of PCEC rabies vaccine was 100 per cent in the tested healthy volunteers. The kinetics of antibody induction after PCEC rabies vaccine is comparable to antibody induction after HDC rabies vaccine. PCEC rabies vaccine induces cellular immunity as measured in lymphocyte transformation test, but no interferon activity.     

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.     

Immunogenicity and safety of purified Vero-cell rabies vaccine in severely rabies-exposed patients in China

The immunogenicity and safety of a purified Vero-cell rabies vaccine (PVRV, VERORAB; Aventis Pasteur, France) were evaluated in 171 patients treated for severe exposure to rabies (WHO category III contacts) at the Shandong Provincial Antiepidemic Station in Jinan and an EPI center in Ping Yin, China. Post-exposure treatment consisted of a single dose of equine rabies immunoglobulin (ERIG, 40 IU/kg body weight) on Day (D) 0, and intra-muscular administration of PVRV on D 0, 3, 7, 14 and 28. Antirabies antibody levels were evaluated on D 0, 7, 14, 28, 90 and 180 using the rapid fluorescent focus inhibition test. By D 14 all subjects had seroconverted (> or = 0.5 IU/ml), with a geometric mean titer of 50.3 IU/ml. Antibody titers remained above the seroprotection threshold in all patients for 3 months, and in 98.2% of subjects for 6 months. All patients were still alive 6 months after the start of treatment. PVRV and ERIG were shown to be well tolerated and no serious adverse events were observed. Following PVRV administration, 12 patients (7.0%) had at least one local reaction (mostly pruritus, erythematous rash and pain). Fourteen patients (8.2%) developed local reactions at the site of ERIG administration. Twelve patients (7.0%) developed systemic reactions following post-exposure treatment, the most frequent of which were pruritus, rash and vertigo. This study demonstrates that PVRV is immunogenic and safe in Chinese patients treated according to WHO recommendations for severe rabies exposure.     

Antibody response after a four-site intradermal booster vaccination with cell-culture rabies vaccine.

The current World Health Organization recommendation for booster vaccination of previously immunized individuals with potential exposure to rabies is two doses of vaccine intramuscularly or intradermally on days 0 and 3. We report responses to two types of postexposure treatment of healthy individuals who had received preexposure rabies vaccination 1 year previously. Group A individuals received four intradermal doses (one-fifth of the diluent volume of vaccine per dose) on day 0, and group B individuals received two intramuscular doses on days 0 and 3. Immunogenicity of the two booster regimens was assessed by titrating the amount of neutralizing antibody (Nab). We found that the booster doses of vaccine produced remarkable responses in all subjects. Nab titers of > or = 0.5 IU/mL (acceptable antibody level for protection against rabies) were detected in all subjects on day 14, and they were shown to be consistently high 1 year after the booster vaccination. We also found that the Nab titers for group A were significantly higher (two- to eightfold) than those for group B on days 5, 14, 150, and 360 after the initial booster vaccination (P < .05). Our study shows that the four-site intradermal booster regimen with use of one-fifth of the diluent volume of cell-culture rabies vaccine on day 0 is associated with a significantly higher antibody response than is the conventional booster regimen for subsequent postexposure rabies treatment of individuals who have received preexposure rabies vaccination with cell-culture rabies vaccine 1 year previously.     

Post-exposure prophylaxis with purified vero cell rabies vaccine during pregnancy--safety and immunogenicity

This study was conducted with the main objective of determining the safety and immunogenicity of purified vero cell rabies vaccine (PVRV) during pregnancy. Twenty nine pregnant women exposed to rabies were vaccinated with PVRV as per the Essen regimen advocated by World Health Organization. None of the women experienced any adverse side effects to the vaccine. The intrauterine growth and development monitored by ultrasound examination was found to be normal and the outcome of pregnancy was satisfactory. There were no congenital anomalies in any of the infants born and they were healthy and had normal growth and development during the one year follow-up period. The rabies neutralizing antibody titers from day 14 to day 365 following vaccination in these women was adequate and well above the minimum protective level of 0.5 iu/ml of serum. Protective levels of antibodies were also present in serum of some of the babies tested, for up to 3 months of age. The mothers and infants followed for one year period were doing well at the end of the study period. Consequently, PVRV was found safe and immunogenically efficacious during pregnancy.     

Antibody responses to human diploid cell vaccine for rabies with and without human rabies immune globulin

One hundred one volunteers with no exposure to rabies were given human diploid cell vaccine (HDCV) for rabies with or without 20 international units of human rabies immune globulin (HRIG)/kg of body weight to evaluate schedules for therapy with HDCV and HRIG after exposure. All of the volunteers who received three or more doses of HDCV alone or four or more doses of HDCV with HRIG developed high titers of neutralizing antibodies by day 35, which persisted for at least 60 days. By day 7, of the 61 volunteers given HRIG and HDCV, 53% had neutralizing antibodies by a mouse neutralization test and 67% had neutralizing antibodies by a rapid fluorescent focus inhibition test. Similar antibody levels were found in volunteers given HRIG alone, a finding which suggests that low or undetectable early titers after administration of HDCV and HRIG were due to inadequate HRIG dosage rather than any interaction between the passive antibody (HRIG) and the vaccine antigen. These results suggest that trials with 30 or 40 international units of HRIG/kg in combination with HDCV are warranted.     

Pre-exposure rabies immunization with human diploid cell vaccine: decreased antibody responses in persons immunized in developing countries

In November 1982, a U.S. Peace Corps volunteer in Kenya completed pre-exposure rabies prophylaxis with a standard 3 dose intradermal (ID) series of human diploid cell rabies vaccine (HDCV). In May 1983, she was bitten by a dog and died of rabies 3 months later. An initial investigation revealed that the patient, as well as 9 of 11 others immunized at the same time, had no rabies antibody titers (less than 1:5). We therefore instituted investigations into the immunogenicity of pre-exposure HDCV both in the United States and in developing countries. A serosurvey revealed unexpectedly low rabies titers in both Peace Corps volunteers and others immunized in developing countries. Antibody titers measured 2-3 weeks after ID immunization were compared in 9 groups totaling 271 persons in the United States and Kenya. There was no statistically significant difference in antibody titers in the 6 U.S. groups immunized from 1980-1984 (P greater than 0.15); however, groups immunized in the United States had significantly higher titers than a group of Kenyan nationals (P less than or equal to 0.0001), and the Kenyans had significantly higher titers than 2 Peace Corps groups immunized in Kenya (P less than or equal to 0.0001). No single hypothesis proposed (laboratory error, vaccine potency, vaccination technique, or specific immune suppression) accounted for the observed differences. Although we cannot fully explain the poor response to HDCV, it is probably due to multiple factors. We conclude that persons immunized with ID pre-exposure HDCV in developing countries should have rabies antibody titers determined to ensure their seroconversion; for persons immunized in the United States, such titers need not be routinely determined.     

Immunization with a human diploid cell strain of rabies virus vaccine: two-year results

Antibody responses following primary vaccination with 1.0 ml of intramuscularly (im) or 0.1 ml of intradermally (id) administered human diploid cell rabies virus vaccine were observered for two years. Three primary doses of vaccine were given to 77 volunteers on days 0, 28, and 56. An antibody response was detected in all vacinees after a single dose; at one month, the response in the group that received vaccine id was identical to that in the group that was given vaccine im, although only 1/10th of the dose of vaccine was used. After the second and third doses, the antibody responses were higher with the primary im regimen; this difference was significant at two, three, and 12 months when the geometric mean titers of antibody were twofold higher for im than for id vaccination. The antibody responses to a booster dose of vaccine administered to randomly grouped volunteers by the subcutaneous or id route at six, 12, or 24 months were similar irrespective of the method of primary immunization but were greater with increasing intervals between primary and booster doses.     

检测狂犬病毒的胶体金免疫层析法的建立及应用

目的 建立一种简易快速、适用于野外的胶体金免疫层析法(GICA)用于检测动物脑或唾液中的狂犬病街毒抗原。方法采用柠檬酸三钠还原法制备胶体金颗粒，标记抗狂犬病毒单抗。制成免疫层析测试条。样品中的狂犬病毒抗原与测试条上金标记抗体结合后沿着硝酸纤维素膜移动，与膜上的固相抗体结合形成肉眼可见的红色线条。结果 GICA测试条只与狂犬病毒抗原有特异性反应，与乙型脑炎病毒、正常小鼠脑组织等无交叉反应。GICA与EIA比较检测了48份可疑狂犬病犬唾液样品，两法的符合率为88．2％。结论 GICA检测样品中的狂犬病毒抗原特异性强、灵敏度高、简便快速、无需仪器设备，对基层单位开展初步鉴定狂犬病毒样品工作而言。不失为一种有效的方法。     

Recovery from rabies in man.

A 45-year-old woman from Mendoza, Argentina, was severely bitten by a dog that died 4 days later. Before death, the dog was nervous, aggressive, and had occasional seizures. Ten days after the woman had been bitten, rabies vaccine treatment was begun: 14 daily doses of suckling mouse brain vaccine followed by 2 booster doses. Twenty-one days after the biting episode, she developed a cerebellar striatal syndrome, which persisted throughout several months, and severe encephalitic symptoms, which persisted for 75 days. After 13 months, recovery was nearly complete. The patient's serum and cerebrospinal fluid contained rabies-neutralizing antibodies reaching maximum titers of 1:640 000 and 1:160 000, respectively. Titers of this magnitude have never been previusly recorded after suckling mouse brain vaccine treatment. This phenomenon, together with the epidemiologic, clinical, and laboratory data presented, supports the conclusion of a nonfatal case of rabies in man.     

The primary hamster kidney cell rabies vaccine: adaptation of viral strain, production of vaccine, and pre- and postexposure treatment

The hamster kidney cell rabies vaccine was investigated as a substitute for classical nervous tissue rabies vaccine. The Beijing strain of fixed rabies virus was adapted to primary hamster kidney cells (PHKCs), and four types of rabies vaccine (plain, adjuvant, concentrated, and concentrated adjuvant vaccines) were developed for human use. The potencies of the vaccines met the requirements of the World Health Organization, and these vaccines elicited rather satisfactory antibody responses in volunteers. The postexposure use of vaccine was evaluated in 301 individuals, 97 of whom had been bitten by proven rabid animals. None of the individuals contracted rabies during the observation period. After several years of field trials with both pre- and postexposure vaccines, the evidence indicates that the PHKC rabies vaccines are effective and safe for human use.     

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.     

A new Vero cell rabies vaccine: results of a comparative trial with human diploid cell rabies vaccine in children.

We evaluated the immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) compared with human diploid cell rabies vaccine (HDCV) after pre-exposure immunizations (both primary and booster). Intramuscular doses of either 0.5 mL of CPRV or 1.0 mL of HDCV were given to 400 schoolchildren on days 0, 7, 28, and 365 (booster). Adequate titers of antibody (> or = 0.15 IU/mL, as defined by the Centers for Disease Control and Prevention) were observed in serum samples from all children 14 days after primary immunization with CPRV and HDCV; the antibodies persisted in all but one child up until 1 year. Fourteen days after the primary immunization series (day 42) and 7 days after booster immunization (day 372), all children had antibody titers of > or = 0.5 IU/mL. Local and systemic reactions after primary and booster immunizations occurred significantly less frequently in the CPRV group. A severe allergic reaction (angioedema) was reported in only one child after booster immunization with HDCV. CPRV has adequate immunogenicity for primary and booster pre-exposure immunizations in children and has a better safety profile than does HDCV.