Chick Embryo Cell Rabies Vaccine Research Articles

Safety of purified chick embryo cell rabies vaccine administered in previously vaccinated animal handlers working in a biological park

Background: Wild animal handlers are at continuous risk of exposure to rabies. They have to be protected against rabies by pre-exposure rabies vaccination and regular booster doses. Methodology: The study was conducted in a biological park in Karnataka during October 2018. Animal handlers working in the various capacities at the park and having taken three primary doses of anti-rabies vaccine as pre-exposure prophylaxis were the study subjects. The booster dose of anti- rabies vaccine was administered by a team of trained vaccinators. After the vaccination all the subjects were observed for any adverse reactions for thirty minutes; subsequently the subjects were followed up for any adverse drug reactions through telephone for a period of 30 days. Results: The study included 198 subjects with a mean age of 38.1 + 12 years. Only 8 adverse reactions were reported from 8 subjects immediately following vaccination. The adverse reactions were itching 3 (1.5%) & redness 5 (2.5%); which subsided without any complications. None of the subjects developed systemic or delayed adverse reactions. Conclusion: Booster dose rabies vaccination with purified chick embryo cell rabies vaccine is safe in previously vaccinated animal handlers.

Clinical evaluation of purified chick embryo cell rabies vaccine administered intradermally in animal exposures

Background: In India, presently there are two purified chick embryo cell culture vaccines (PCECV) viz., Rabipur (Flury LEP strain) and Vaxirab – N (Pitman Moore strain) which are commonly used both in public as well as private sectors. The present study was conducted to assess the clinical efficacy in terms of safety, immunogenicity and survival status of both the PCECV administered animal exposures taking complete PEP at the anti-rabies clinic.Methods: A longitudinal study was conducted at the anti-rabies clinic, Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. 86 suspect rabid dog bite cases attending clinic were enrolled and followed up for 1year. All the animal bite cases were given post exposure prophylaxis of full course of PCECV i.e. Rabipur or Vaxirab - N as per schedule intradermally using updated Thai Red Cross regimen. The rabies virus neutralizing antibody (RVNA) concentrations on days 14, 28, 90, and 180 were tested by modified rapid fluores­cent focus inhibition test.Results: Out of 86 study subjects, 43 subjects received Rabipur and another 43 subjects received Vaxirab –N vaccines. The incidence of adverse drug events (ADEs) was found to be 9.3%. All subjects had protective RVNA titers of ³0.5 IU/ml from day 14 till day 180. All the study subjects were healthy and alive after 6 months of completing PEP.Conclusions: The currently available purified chick embryo cell culture rabies vaccines are safe, immunogenic and clinically effective for post exposure prophylaxis in animal bite cases, which will help in eliminating human rabies by 2020.

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.

Comparison of the immunogenicity and safety of the purified chick embryo cell rabies vaccine manufactured in India and Germany: A randomized, single blind, multicentre, phase IV clinical study

ABSTRACTThis phase IV, single blind study assessed the immunogenicity and safety of India-manufactured purified chick embryo cell rabies vaccine (PCECV), compared with a German-manufactured batch obtained by the same production process. A total of 340 participants enrolled at 2 study sites in India were randomized (1:1:1:1) in 4 groups to receive a 5-dose Essen regimen with either 1 of the 3 Indian batches (PCECV-I) or the German batch (PCECV-G), administered on Days (D) 0, 3, 7, 14 and 30. The lot-to-lot consistency of PCECV-I batches in terms of induced immune response at D14 was demonstrated. The immune response elicited by PCECV-I was shown to be non-inferior to that induced by PCECV-G, as the lower limit of the 95% confidence interval for the ratio (PCECV-I/PCECV-G) of rabies virus neutralising antibody (RVNA) geometric mean concentrations was higher than 0.5 at D14. At least 96% of participants developed adequate RVNA concentrations (≥ 0.5 IU/mL) by D14 and all achieved RVNA concentrations ≥ 0.5 IU/mL by D90. RVNA levels were comparable across all groups throughout the entire study. Solicited local and general symptoms had a similar incidence in all groups. Unsolicited adverse events (AEs) were reported by 11% of participants. Only 1 serious AE (leg fracture) was reported and was not related to vaccination. No deaths and no rabies cases were recorded during the 90 days of observation. The study showed that the 3 PCECV-I and the PCECV-G batches induced a similar immune response and had a comparable safety profile when administered according to a 5-dose schedule.

Safety of intradermal rabies vaccine as pre-exposure prophylaxis among veterinary students

Background: Animal bites are a major public health problem in our country. Pre-exposure vaccination using cell culture vaccines is a safe and effective method of preventing rabies and is recommended for anyone who will be at continual, frequent or increased risk of exposure to the rabies virus, as a result of their occupation, such as veterinarians, animal handlers and laboratory workers dealing with any lyssaviruses. The present study was done to assess the safety of purified chick embryo cell rabies vaccine administered as pre-exposure regimen.Methods:The present study assessed the safety of purified chick embryo cell rabies vaccine administered as a 3 dose intradermal pre-exposure vaccination in healthy volunteered veterinary students of Government Veterinary College, Bangalore. Results: 122 apparently healthy adults of both sex, between 18 and 30 years of age were enrolled in the study and 105 (86%) completed all three doses. A total of 342 doses of intradermal vaccine were administered, among which 38 adverse reactions were reported from 19 veterinary students. The adverse reactions were pain at the injection site 7 (2.1%), redness 13 (3.8%), itching at the site of injection 11 (3.2%), induration 6 (1.8%) and headache 1 (0.3%). All reactions subsided without any complication and none of them dropped out from the study because of any adverse drug reactions. Conclusions:Pre-exposure vaccination is a useful tool for protecting high risk groups and purified chick embryo cell rabies vaccine has proved to be safe and well tolerated by intradermal route.

Safety of Intradermal Rabies Vaccination as Pre Exposure Prophylaxis

Need for the study: WHO recommends pre exposure prophylaxis in rabies endemic countries for all individuals who are at increased risk of exposure to rabies such as veterinarians, rag-pickers, animal handlers, rabies researchers/laboratory workers, International travellers and children. Objectives: To assess the safety of rabies vaccine administered intradermally as pre-exposure prophylaxis among 3 high risk groups viz., children, rag-pickers and veterinarians. Methods: All the subjects who volunteered from each of the 3 risk groups were taken for the study and were given purified chick embryo cell rabies vaccine having a potency of >2.5 IU per dose, intradermally as pre exposure prophylaxis on days 0, 7 and 21. Subsequently, all were followed up to assess the safety of intradermal rabies vaccination by recording the adverse drug reactions from the day of administration of first dose of vaccination upto 2 weeks after the last dose of vaccination. Results: The present study included 150 children, 225 rag-pickers and 122 veterinary students. The adverse drug reactions to rabies vaccination among these groups were 5.1%, 5.0% and 10.4% respectively which were mild in nature and subsided spontaneously or by taking symptomatic treatment and none of the subjects dropped out because of adverse drug reactions. Conclusion: Pre exposure prophylaxis against rabies by intradermal route is safe and well tolerated by high risk groups, which may be considered as a strategy for eliminating the disease by 2030.

Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (PCECV) administered according to two different simulated post exposure intramuscular regimens (Zagreb versus Essen)

Despite availability of effective rabies vaccines, India has the highest global mortality rate for rabies. Low socio-economic communities are most affected due to lack of awareness of the disease and poor compliance to post-exposure prophylactic regimens. Currently, the only approved intramuscular regimen for post-exposure prophylaxis (PEP) against rabies in India is the Essen regimen, which consists of 5 injections administered over 5 separate days in a period of one month. The high number of doses and clinical visits, however, are major reasons for non-compliance, and thus a shorter regimen would be beneficial. In a simulated PEP trial in healthy, adult subjects, this study evaluated whether purified chick embryo cell vaccine (PCECV), administered according to the WHO-recommended 4-dose/3 visit Zagreb vaccination regimen is of equal immunogenicity and safety as the standard Essen regimen in Indian subjects. Two hundred and 50 healthy adults were enrolled and randomized into a Zagreb or Essen group, each receiving PCECV according to their respective regimen. Blood samples were collected on Days 0, 7, 14 and 42 and analyzed using the rapid fluorescent focus inhibition test (RFFIT). By Day 14, all subjects across both groups attained rabies virus neutralizing antibody (RVNA) concentrations of ≥ 0.5IU/ml. The Zagreb regimen was then demonstrated to be immunologically non-inferior to the Essen regimen by Day 14, which was the primary endpoint of the study. No safety issues were noted and the occurrence of adverse events was similar in both groups (17% and 15%, respectively). NCT01365494. CTRI No.: CTRI/2011/07/001857

Immunogenicity and safety of purified chick-embryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: A randomized open-label study

The aim of this Phase IIIb, open-label, randomized study was to demonstrate the non-inferiority of immune responses and to assess the safety of a purified chick-embryo cell rabies vaccine (PCECV) in healthy Chinese children (6 to 17 years) and older adults (≥51 years) following 2 alternative intramuscular (IM) simulated post-exposure prophylaxis (PEP) regimens: 4-dose Zagreb or 5-dose Essen regimen. Serum samples were collected prior to vaccination on Days 1 and 15 and on day 43 to assess immune response by rabies virus neutralizing antibody (RVNA) concentrations. Solicited adverse events (AEs) were recorded for up to 7 days following each vaccine dose, and unsolicited AEs throughout the entire study period. PCECV vaccination induced a strong immune response at Day 15, and the non-inferiority in immune response of the Zagreb vs. the Essen regimen was demonstrated in children and older adults. At Day 15,100% of children (N = 224), and 99% of subjects ≥51 years of age (N = 376) developed adequate RVNA concentrations (≥0.5 IU/mL); at Day 43 all subjects achieved RVNA concentrations ≥0.5 IU/mL, for both PEP regimens. The well-known tolerability and safety profile of the PCECV was again observed in this study following either Zagreb or Essen regimens. Rabies PEP vaccination with PCECV following a Zagreb regimen induced immune responses non-inferior to those of the Essen regimen, and had a similar safety and tolerability profile to the Essen regimen in Chinese children, adolescents, and adults over 51 years. ClinicalTrials.gov identifier: NCT01680016.

A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults

The Zagreb regimen has been used for 20 years in various countries. In China, until 2010, the Zagreb schedule was only approved for purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccines (PVRV). In this phase III clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the Zagreb regimen compared with the Essen regimen in healthy adult Chinese immunized with PCECV (Rabipur®). The study enrolled 825 subjects aged 18 to 50 years; serum samples were collected on Days 0, 7, 14, 42, and at 13 months to assess rabies virus neutralizing antibody (RVNA) concentrations. Solicited and unsolicited local and systemic reactions were recorded for 6 days following the day of vaccination, and collected throughout the entire study period (Day 1 until Month 13). The Zagreb regimen was non-inferior to the Essen regimen with regard to RVNA concentrations after 7, 14, and 42 days, and 13 months of immunization. The non-inferiority of seroconversion was established at Days 14 and 42. The incidence of local and systemic reactions was similar between groups, and mostly of mild or moderate severity. Vaccine-related adverse events occurred more frequently in the Essen group than in the Zagreb group. Vaccination with PCECV under a 2-1-1 regimen is as safe and immunogenic as under the traditional 5-dose Essen regimen for rabies post-exposure prophylaxis, and is a more cost-effective option, has a more practical vaccination schedule, and can potentially increase compliance.

Safety and Immunogenicity of purified chick embryo cell rabies vaccine (VaxiRab N) administered intradermally as post exposure prophylaxis

The affordability to rabies vaccine for intramuscular administration in post exposure prophylaxis is a major constraint. Therefore, in countries, where there are financial constraints, World Health Organization recommends intradermal rabies vaccination that reduces the quantity and cost of vaccination. This study was done to evaluate the safety and immunogenicity of indigenously developed rabies vaccine (VaxiRab N) in comparison to a WHO recommended rabies vaccine (Rabipur) with demonstrated efficacy when administered by intradermal route using updated Thai Red Cross regimen. Eighty-six dog bite cases were randomly given either VaxiRab N (n = 43) or Rabipur (n = 43) as post exposure prophylaxis. The rabies virus neutralizing antibody concentrations on days 14, 28, 90, and 180 were tested by modified rapid fluorescent focus inhibition test. The geometric mean RVNA concentration of both the groups were compared using t- test and was found that, P value > 0.05 on all days, thus showing no significant difference between the 2 groups. The adverse drug events were also compared using Z-test and was found to be not statistically significant (Z = 1.476, P = 0.139). In conclusion, VaxiRab N was found to be safe and effective in post exposure prophylaxis by intradermal route and was similar to the WHO recommended rabies vaccine (Rabipur) of demonstrated efficacy.

Pre-exposure prophylaxis against rabies in children

Animal bites in humans are a public health problem. Children are the most frequently exposed, representing 50% of human exposures in canine rabies infected areas. Pre-exposure vaccination using cell culture vaccines is a safe and effective method of preventing rabies among children in these highly endemic regions. The development of immunological memory after pre exposure vaccination has established long lasting immunity against rabies in humans. The present study assessed the safety of Purified Chick Embryo cell Rabies Vaccine (Vaxirab N) administered as a three-dose intradermal pre-exposure regimen on days 0, 7, and 21 in healthy volunteered children of 5–10 y age group from an urban poor locality in Bangalore, India. One hundred fifty three apparently healthy children of both sexes between 5 and 10 y of age were enrolled in the study and 123 (80.4%) completed all three doses. A total of 405 doses of intradermal vaccine was administered, among which 25 adverse reactions were reported from 17 children. The adverse reactions were pain at the injection site 15 (3.7%), redness 2 (0.5%), itching at the site of injection 1 (0.2%), fatigue 1 (0.2%), fever 3 (0.7%), myalgia 2 (0.5%) and allergy 1 (0.2%). All reactions subsided without any complication. In conclusion, pre exposure vaccination against rabies is a useful tool for protecting children living in highly endemic regions and Vaxirab N has proved to be safe and well tolerated by intradermal route among children.

Safety and immunogenicity study of a new purified chick embryo cell rabies vaccine Vaxirab-N (Pitman–Moore strain) manufactured in India

Zydus Cadila Health care, India developed a new purified chick embryo cell rabies vaccine (PCECV, Vaxirab-N; 1 mL) by adapting Pitman–Moore strain of virus on to the chick embryo fibroblast cell line in 2006. During 2007–10, a series of safety and immunogenicity studies were conducted as per ICH-GCP guidelines after obtaining permission from Drug Controller General of India. In the first study, Vaxirab-N was administered to 35 healthy adult volunteers by intramuscular (IM) route using pre exposure regimen. The geometric mean concentration (GMC) of rabies virus neutralizing antibody (RvnAb) of 7.5 IU/mL on day 35. In the second study, Vaxirab-N was administered to 35 healthy adult volunteers using simulated post- exposure prophylaxis regimen by IM route. A GMC of 6.3 IU/mL on day 14, 13.2 IU/mL on day 28 and 8.6 IU/mL on day 90 was obtained. In the third study, Vaxirab-N administered by intradermal (ID) route using Updated Thai Red Cross (TRC) regimen in 36 healthy adult volunteers showed GMC of 7.8 IU/mL on day 14, 11.5 IU/mL on day 28 and 6.0 IU/mL on day 90. The 4th study was multi centric and Vaxirab-N was administered to 129 animal bite cases by IM route using post-exposure Essen regimen. The GMC following this schedule was 8.2 IU/mL on day 14, 13.01 IU/mL on day 28, 7.92 IU/mL on day 90 and 3.72 IU/mL on day 180. Mild to moderate adverse events were reported to Vaxirab-N but no serious adverse events were reported in any of these studies. In conclusion, Vaxirab-N developed by Zydus Cadila was found to be safe and immunogenic by both intramuscular and intradermal route and is recommended for rabies prophylaxis (CTRI No. 2010/091/000055 and 2010/091/000509).

Post Vaccination Myelitis in a Young Woman Following Administration of Rabies Chick Embryo Cell Vaccine - A Case Report

A case of post-vaccination myelitis following administration of chick embryo cell rabies vaccine in a 20 year-old young lady is described. The case presented with paraplegia five days after receiving the third dose (on 12th day) of the vaccine for rabies. Myelitis was confirmed by signal changes on magnetic resonance imaging (MRI). She improved considerably on steroids treatment. This is the first case of myelitis following rabies chick embryo cell vaccination in Bangladesh. DOI: http://dx.doi.org/10.3329/imcj.v6i2.14738 Ibrahim Med. Coll. J. 2012; 6(2): 76-77

Evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: Results of a randomized, open label, active-controlled trial in healthy adult volunteers in India

The currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. There is a need to introduce and evaluate short course regimens to overcome this problem. This study was conducted to evaluate the immunogenicity and safety of a “new one week intradermal regimen” for rabies post-exposure prophylaxis. A total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick embryo cell (PCECV) rabies vaccine or purified verocell rabies vaccine (PVRV), 40 in each group. Each subject received intradermally one of the vaccines, using the one week regimen (4–4-4). Blood samples were collected on Days 0, 7, 14, 28,180 and 365 for estimation of rabies virus neutralizing antibody (RVNA) concentration. The sera samples were analyzed by rapid fluorescent focus inhibition test (RFFIT). All subjects in both the groups had adequate RVNA concentration of ≥ 0.5 IU/mL from day 14 to till day 180 and the difference of geometric mean concentrations between the two groups was not significant (p > 0.606). Further to assess the immunological memory produced by this new regimen, a “single visit four site” intradermal booster vaccination was given to those who did not have adequate RVNA concentration on day 365. This resulted in a quick and enhanced RVNA concentration in these subjects thus denoting a successful anamnestic response. The incidence of adverse events was 8.3% in PCECV group and 1.6% in PVRV group (p = 0.001) and the regimen was well tolerated without any dropouts. In conclusion, the new “one week intradermal regimen” is immunogenic and safe for rabies post-exposure prophylaxis and needs to be further evaluated in persons exposed to rabies.

Immunogenicity of intradermal vaccination of Japanese rabies vaccine for preexposure immunization following WHO recommendation

In the present study, we evaluated the immunogenicity of intradermal vaccination of Japanese purified chick embryo cell rabies vaccine (PCEC-K) for preexposure immunization (PEI). A total of 39 healthy subjects were administered a single 0.1-ml dose of PCEC-K intradermally at the antebrachial region on days 0, 7, and 28. To assess immunogenicity, rabies neutralizing antibody (NA) titers were measured on days 7, 28, and 42 post vaccination. By day 42, all subjects developed NA titers ≥0.5 IU/ml (geometric mean titer, 2.7 IU/ml), a level that is considered protective. The vaccine was well tolerated; vaccinated subjects displayed minimal redness and pruritus. Although a 1.0-ml dose of PCEC-K administered subcutaneously is considered the standard method, the intradermal regimen using a 0.1-ml dose of PCEC-K is immunogenic, safe, and highly recommended for situations of vaccine shortage.

Pre-exposure immunization against rabies using Japanese rabies vaccine following the WHO recommended schedule

We examined the efficacy and safety of the Japanese purified chick embryo cell rabies vaccine (PCEC-K) when administered on days 0, 7, and 28, as recommended by the WHO. Post-vaccination serum samples were obtained from 53 human subjects, and rabies antibody titers were determined by a combination of enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody (NA) assay. By day 42 of the experiment, which was 2 weeks after the third dose, all subjects had developed NA titers of 0.5 IU/ml or higher. The geometric mean titers of ELISA antibody and NA were 3.8 EU/ml and 5.7 IU/ml, respectively. Overall, the vaccine was well tolerated by all subjects. These results suggest that PCEC-K used for pre-exposure immunization according to the WHO schedule is as immunogenic and effective as the current pre-exposure immunization regimen in Japan, which consists of vaccines administered on days 0, 28, and 180. An accelerated schedule would be of great advantage to Japanese travelers, who could complete the required three doses for primary immunization in 1 month.

A Three-Year Clinical Study On Immunogenicity, Safety, and Booster Response of Purified Chick Embryo Cell Rabies Vaccine Administered Intramuscularly or Intradermally to 12- to 18-Month-Old Thai Children, Concomitantly With Japanese Encephalitis Vaccine

After concomitant administration of purified chick embryo cell rabies vaccine and Japanese encephalitis vaccine to toddlers, adequate rabies and Japanese encephalitis virus neutralizing antibodies concentrations were demonstrated by day 49, 7 days after a booster at 1 year, and in the majorly at 3 years postvaccination. The inclusion of rabies vaccine in the expanded program on immunization should be considered in rabies endemic countries.

Safety review of the purified chick embryo cell rabies vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS), 1997–2005

On October 20, 1997, the U.S. Food and Drug Administration (FDA) licensed Purified Chick Embryo Cell (PCEC, RabAvert®) vaccine against rabies in humans following clinical trials demonstrating safety and efficacy. From October 1997 through December 2005, the Vaccine Adverse Event Reporting System (VAERS) received 336 reports of adverse events (AEs) following vaccination with PCEC vaccine in the U.S.; there were no death reports. Serious events, including 20 hospitalizations and 13 neurological events, were described in 24 (7%) reports. There was no pattern among the 13 neurological AEs suggesting a plausible relationship to vaccination. A total of 20 AEs, 3 serious, were classified as possible anaphylaxis. There were 312 non-serious AEs (93%). Nineteen reports (6%) described that the vaccination series was discontinued because of non-serious AEs. Most reported AEs are non-serious and consistent with pre-licensure safety data. The rabies risk must be carefully considered before vaccine discontinuation.

The influence of homologous vs. heterologous challenge virus strains on the serological test results of rabies virus neutralizing assays

The effect that the relatedness of the viral seed strain used to produce rabies vaccines has to the strain of challenge virus used to measure rabies virus neutralizing antibodies after vaccination was evaluated. Serum samples from 173 subjects vaccinated with either purified Vero cell rabies vaccine (PVRV), produced from the Pittman Moore (PM) seed strain of rabies virus, or purified chick embryo cell rabies vaccine (PCECV), produced from the Flury low egg passage (Flury-LEP) seed strain of rabies virus, were tested in parallel assays by RFFIT using a homologous and a heterologous testing system. In the homologous system, CVS-11 was used as the challenge virus in the assay to evaluate the humoral immune response in subjects vaccinated with PVRV and Flury-LEP was used for subjects vaccinated with PCECV. In the heterologous system, CVS-11 was used as the challenge virus in the assay to evaluate subjects vaccinated with PCECV and Flury-LEP was used for subjects vaccinated with PVRV. Although the difference in G protein homology between the CVS-11 and Flury-LEP rabies virus strains has been reported to be only 5.8%, the use of a homologous testing system resulted in approximately 30% higher titers for nearly two-thirds of the samples from both vaccine groups compared to a heterologous testing system. The evaluation of equivalence of the immune response after vaccination with the two different vaccines was dependent upon the type of testing system, homologous or heterologous, used to evaluate the level of rabies virus neutralizing antibodies. Equivalence between the vaccines was achieved when a homologous testing system was used but not when a heterologous testing system was used. The results of this study indicate that the strain of virus used in the biological assays to measure the level of rabies virus neutralizing antibodies after vaccination could profoundly influence the evaluation of rabies vaccines.

Evaluation of a new five-injection, two-site,intradermal schedule for purified chick embryo cell rabies vaccine: A randomized, open-label, active-controlled trial in healthy adult volunteers in India

Background: Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. Objective: The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India. Methods: This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 [“2-2-2-2-2”]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test. Results: Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group and none in the IM group; P = 0.026). All of the AEs were transient and resolved without the need for medication. All subjects had serum RVNA concentrations ≥0.5 IU/mL—considered protective by the World Health Organization—at all follow-up visits. However, the mean RVNA concentrations in the IM group were significantly higher compared with those in the ID group from days 14 to 365 (all, P < 0.001). Conclusion: In this study in healthy volunteers, PEP with PCECV administered using the KIMS-ID regimen was well tolerated and immunologically efficacious for 365 days. Adequate RVNA levels were maintained with the KIMS-ID regimen from days 14 to 365, although these levels were significantly lower than those achieved in the group receiving the Essen IM regimen (all, P < 0.001).