Cell-mediated immune response following intracutaneous immunisation with human diploid cell rabies vaccine

Specific cell-mediated immune response (CMIR) against rabies antigens was studied in recipients of two regimens of human diploid cell rabies vaccine (HDCV) using the antigen-stimulated lymphocyte transformation test (LTT) as a measure of CMIR. Reconstituted HDCV could be conveniently used as the in vitro stimulating antigen and the response was antigen-dependent. Conventional intramuscular immunization with full-dose HDCV resulted in positive LTT as early as 14 days after starting immunisation, and peaked on day 28. Intracutaneous immunisation with 0.1 ml of HDCV at four sites on days 0, 3 and 7 was a more efficient means of inducing specific lymphocyte response. Specific CMIR was evident as early as seven days and became maximal on day 14. In addition to the more rapid induction of specific CMIR, our intracutaneous regimen also resulted in a brisker and higher antibody response than the intramuscular regimen. The peak antibody level of the intracutaneous regimen was reached on day 14 whereas that of the intramuscular regimen was reached on day 28 and the geometric mean antibody titre on day 14 of the intracutaneous route was significantly higher than that of the intramuscular regimen. We therefore conclude that our closely spaced intracutaneous immunisation with HDCV was effective both in the induction of specific antibodies and the cell-mediated immune response.     

An effective economical intradermal regimen of human diploid cell rabies vaccination for post-exposure treatment.

A closely-spaced multisite intradermal regimen of human diploid cell rabies vaccine (HDCV) was evaluated in 39 patients after low-risk exposure to rabies, in comparison to full-dose intramuscular HDCV and sheep brain-derived rabies (Semple) vaccine. The regimen consisted of four intradermal injections, 0.1 ml each of HDCV on days 0, 3 and 7, followed by two booster doses of only 0.1 ml each on days 28 and 91 administered intradermally. Although the total amount of HDCV used in this intradermal regimen was 1.4 ml or one-quarter of the conventional intramuscular regimen, a higher proportion of the recipients of this economical intradermal regimen, as compared to the full-dose intramuscular regimen, developed neutralizing antibodies above the hypothetical protective level of 0.5 iu/ml 7 days after starting immunization. Besides the earlier antibody response, the peak antibody level of the intradermal regimen was also satisfactorily high and not significantly different from that after the intramuscular regimen. Simultaneous administration of inosiplex, an antiviral and immunopotentiating agent, during the first 10 days of intradermal immunization resulted in an even higher antibody response for as long as 91 days. In contrast, but not unexpectedly, Semple vaccine evoked lower, more sluggish and inconsistent antibody responses. The side-effects of intradermal HDCV were mild, mainly local and self-remitting. We therefore recommend our intensive intradermal regimen of HDCV vaccination for safe, effective and economical use in post-exposure rabies immunization.     

Rabies and post-exposure prophylaxis in Thai children

Thailand is an endemic area for rabies, with approximately 300 human deaths reported annually. More than half of the rabies patients are children under 14 years of age. This paper reports clinical data of paediatric rabies cases occurring from 1980 to 1986, and the protective efficacies of human diploid cell rabies vaccine (HDCV) and purified Vero cell rabies vaccine (PVRV) in children exposed to rabid animals. The analysis of 120 medical records revealed that rabies in children had incubation periods which ranged from less than fifteen days to more than three months, but generally between one to three months. The most frequent symptoms observed in the patients were hydrophobia, restlessness, fever, vomiting and aerophobia. Most of the rabid children admitted to hospital died within 24 hours. HDCV was administered to 50 children exposed to rabies with the cumulative dosages of 327 ml. All patients survived without serious adverse effects during a-two year follow-up. Mild reactions were seen in 1.5 percent (5/327 doses). Unfortunately, levels of rabies antibody in these vaccinees were not determined. Among another series of children exposed to rabid animals, comprising 27 individuals who received a total of 168 doses of PVRV, only mild local reactions were seen in 6 subjects. No rabies deaths were reported in 2 years of follow-up. The children who received PVRV either with or without human rabies immune globulin developed similar levels of rabies neutralizing (NT) antibody, which reached the high titers on day 30. At one year after the first dose of vaccination, all vaccinees still had NT antibody at titers higher than 0.5 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of human immune responses to purified Vero cell and human diploid cell rabies vaccines by using two different antibody titration methods.

Antibody responses to a conventional rabies preexposure regimen of a new purified Vero cell rabies vaccine (PVRV) and a human diploid cell vaccine (HDCV) were compared in 80 healthy Kenyan veterinary students. Forty-three of the students received the PVRV and 37 received the HDCV on days 0, 7, and 28. Antibody responses were monitored by using the rapid fluorescent-focus inhibition test (RFFIT) and an inhibition enzyme immunoassay (INH EIA) on days 0, 7, 28, and 49. Both vaccines elicited a rapid antibody response. A good correlation between the RFFIT titers and the INH EIA titers was obtained (r = 0.90). Our results also showed that the INH EIA was more reproducible and might therefore be a suitable substitute for the more expensive and less reproducible RFFIT. The geometric mean titers determined by both tests in the two groups of students were statistically similar during the test period. The RFFIT and the INH EIA gave comparable geometric mean titers, which differed significantly only on day 28 in the PVRV group. The effect of the new PVRV is comparable to that of the more expensive HDCV, as determined by the present test systems. The PVRV could therefore be the vaccine of choice, especially in tropical rabies-endemic areas, where the high cost of the HDCV has confined its use to a privileged few.     

Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine

We conducted a randomized controlled trial to evaluate the antibody response of freshman veterinary students to intradermal human diploid-cell rabies vaccine administered concurrently with chloroquine, a drug frequently used for chemoprophylaxis against malaria. Fifty-one students who had not been vaccinated against rabies were enrolled: 26 received 300 mg of chloroquine base per week (the recommended dose for malaria prophylaxis); 25 did not receive chloroquine and served as controls. All subjects received 0.1 ml of rabies vaccine intradermally on days 0, 7, and 28. Chloroquine was administered weekly to the treatment group, beginning nine days before the first dose of vaccine and continuing until day 48. The mean rabies-neutralizing antibody titer for the chloroquine group was significantly lower than that for the control group on each day of testing--i.e., day 28 (P = 0.0094), day 49 (P = 0.0008), and day 105 (P = 0.0002)--although both groups had neutralizing antibody titers on days 49 and 105, according to the criteria of the Centers for Disease Control. The blood concentrations of chloroquine and desethylchloroquine (the major metabolite of chloroquine, which also has antimalarial properties) were negatively associated with log antibody titers. These results indicate that chloroquine taken in the dose recommended for malaria prophylaxis can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine.     

Pre-exposure vaccination with purified chick embryo cell rabies vaccines in children

Children who have close contact with rabid dogs, with a history of neither being bitten nor scratched nor licked on broken skin or on mucous membranes were given purified chick embryo rabies vaccine as pre-exposure prophylaxis. Thirteen children received 0.5 ml of the vaccine, while 12 children received 1 ml of the vaccine intramuscularly on days 0, 7 and 28. The rabies antibody level was measured by a standard mouse neutralization test. Before vaccination, all vaccinees had no detectable level of antibody to rabies. On day 14, all children had antibody levels higher than 0.5 IU/ml; the titer peaked from day 28 to day 56 and then was lower on day 90. Children of the 1 ml group had antibody levels higher than the 0.5 ml group, but there was no statistically significant difference. No serious reaction occurred. At 2-3 years of follow up, all children were doing well.     

Induction of protective serum meningococcal bactericidal and diphtheria-neutralizing antibodies and mucosal immunoglobulin A in volunteers by nasal insufflations of the Neisseria meningitidis serogroup C polysaccharide-CRM197 conjugate vaccine mixed with chitosan

Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis serogroup C polysaccharide (MCP)-CRM197 conjugate vaccine in alum or two nasal insufflations 28 days apart of the same vaccine powder, without alum, mixed with chitosan. Nasal immunization was well tolerated, with fewer symptoms reported than after intramuscular injection. The geometric mean concentrations of MCP-specific immunoglobulin G (IgG) after one nasal immunization were 3.25 microg/ml in na?ve subjects and 14.4 microg/ml in subjects previously immunized parenterally, compared with 4.30 microg/ml in na?ve subjects immunized intramuscularly. The geometric mean titer of serum bactericidal antibody (SBA) rose 24-fold after two nasal immunizations in na?ve subjects and was comparable to parenteral immunization (1,080 versus 1,625). All subjects achieved SBA titers associated with protection after two nasal immunizations: even those with titers of <8 at entry. A single nasal immunization boosted the SBA titer to > or =128 in 96% of previously immunized subjects, and two immunizations achieved this level in 92% of naive subjects. MCP-specific IgG levels were approximately 70% IgG2 and approximately 20% IgG1 after nasal or intramuscular immunization. Increases in CRM197-specific IgG and diphtheria toxin-neutralizing activity were observed after nasal or intramuscular immunization, with balanced IgG1/IgG2 and higher IgG4. Significant MCP-specific secretory IgA was detected in nasal wash only after nasal immunization and predominantly on the immunized side. Simple nasal insufflation of existing MCP-CRM197 conjugate vaccines in chitosan offers an inexpensive but effective needle-free prime and boost against serogroup C N. meningitidis and diphtheria.     

Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain

Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD₅₀ rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2 IU/ml and total RVNA titer was observed to be 4 IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD₅₀ of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries.     

Persistence of rabies antibody 5 years after postexposure prophylaxis with vero cell antirabies vaccine and antibody response to a single booster dose

This study was done to investigate the antibody response to a Vero cell antirabies vaccine, the persistence of antibody for 5 years, and the effect of a booster dose after this interval. From August 2005 to February 2011, a total of 195 patients were enrolled into our study due to an animal bite. The Essen intramuscular (i.m.) regimen, which is recommended by the WHO for modern vaccines used in postexposure treatment, was adopted in this study. Blood samples were obtained on day 0, day 7, day 14, day 45, year 1, year 2, year 3, year 4, year 5, and year 5 plus 14 days. Immunogenicity was evaluated by the titration of neutralizing antibodies with a rapid fluorescent focus inhibition test (RFFIT). Seroconversion was expressed as the seroconversion rate (SCR). A secondary quantitative evaluation criterion, other than the seroconversion level, was the geometric mean titer (GMT). Of the 195 enrolled patients, 168 (86.4%) of them completed the whole study. No serious adverse reactions to the vaccine were reported during vaccination, the 5-year follow-up period, or revaccination. On day 14, the rabies antibody GMT value was 8.87 IU/ml in the vaccinees. During the next 5 years, the SCR in the ChengDa vaccine group gradually decreased to 34.0% at year 5, down from 90.5% at year 1. There was a significant booster effect: the GMT was 15.22 IU/ml on year 5 plus 14 days. Our findings demonstrate that the ChengDa rabies vaccine offers an alternative with a high degree of efficacy and yet limited side effects and ensures that the exposed patient will be on the safe side of the risk of rabies by the 14th day. Moreover, when followed by a booster dose 5 years later, it could boost the immunity. A further booster is effective in inducing a good neutralizing antibody response even after an interval of 5 years.     

Comparison of two hepatitis B vaccines (GeneVac-B and Engerix-B) in healthy infants in India

Hepatitis B is a major problem in many parts of the world. The WHO has recommended the inclusion of hepatitis B vaccines in routine immunization schedules. We wanted to compare two recombinant hepatitis B vaccines in an infant population for immunogenicity and reactogenicity when given at 6, 10, and 14 weeks of age. One hundred seventy-three infants meeting eligibility criteria were given either GeneVac-B (Serum Institute of India Ltd.) or Engerix-B (GlaxoSmithKline Beecham) in a random fashion. Three 0.5-ml (10-mug) doses of the vaccines were given at 6, 10, and 14 weeks of age along with diphtheria-pertussis (whole cell)-tetanus (DTPw) vaccine. Blood samples were collected at baseline and 1 month after administration of the third dose of the vaccines to measure anti-HBs antibody levels. Seroconversion was defined as a titer of more than 1 x 10(-3) IU/ml, while seroprotection was defined as a titer of more than 10 x 10(-3) IU/ml. Of the GeneVac-B recipients, 98% seroconverted versus 99% of the Engerix-B group. The anti-HBs geometric mean titer was slightly greater for GeneVac-B (229 x 10(-3) IU/ml) than for Engerix-B (167 x 10(-3) IU/ml), but the difference was not significant. The seroprotection rates were similar for both vaccines (96% and 95%, respectively). The most common systemic reaction events were mild to moderate fever, excessive crying, local swelling, rash, and irritability, and the local reactions were redness, induration, and edema, which most probably were caused by the simultaneously administered DTPw vaccine. All events were transient and resolved without sequelae. Reactogenicity was similar for the two vaccines. The present study shows that GeneVac-B is as immunogenic and as well tolerated as Engerix-B when administered with DTPw vaccine at 6, 10, and 14 weeks of age.     

Seroprevalence of tetanus antibody in the Thai population: a national survey

Tetanus is a disease with high mortality and the most important measure for effective prevention is vaccination. Tetanus immunization has been introduced to Thailand's national immunization program for 30 years. Yet, the coverage and seroprevalence of tetanus antibody in vast parts of the population has not been assessed. This study has been performed on 1,277 subjects aged between 6 months and 60 years or above from four geographically distinct provinces of Thailand. Tetanus antibody levels were measured using a commercially available ELISA kit. Most of the Thai population had immunity against tetanus. The level of antibodies to tetanus, as demonstrated by the geometric mean titer of antibody (GMT) (and 95% confidence interval) was 2.62 (2.34-2.91) IU/ml. The highest and lowest GMT was found in subjects aged between 5 and 9 years, and above 60 years of age with GMT (and 95% confidence intervals) of 3.64 (3.34-3.96) and 1.24 (0.67-2.29) IU/ml respectively. The minimum protective level of antitoxin (>0.01 IU/ml) was detected in 99.7 % of subjects. More than 90% of subjects displayed durable antibody protection levels (DAPL) (> or = 1.0 IU/ml), except for subjects above the age of 60 years (82%). According to this study, the majority of the population expresses tetanus antibody levels that can confer long term protection. Yet, considering the lowest GMT and the highest incidence of tetanus cases found in subjects aged above 60 years, re-immunization should be targeted at this age group especially if they had sustained any tetanus-prone injury.     

西尼罗病毒与乙脑病毒免疫交叉反应的实验研究

为明确西尼罗病毒(WNV)与乙型脑炎病毒(JEV)的免疫交叉反应,本文分别用WNV全抗原与JE减毒活疫苗免疫小鼠,采用间接免疫荧光试验检测血清中2种病毒IgG抗体水平及其交叉反应情况。结果表明:WNV组在第4次免疫后的14天和35天出现2个高峰,平均效价分别为6088和4305;JEV组第4次免疫后,小鼠血清JEV抗体呈现缓慢上升的趋势。无论是在WNV全抗原免疫小鼠血清中还是在JE减毒活疫苗免疫小鼠血清中,同一血清对WNV抗原和JEV抗原均有反应,且抗体效价差异有显著性。在抗WNV抗体阳性血清中,两者交叉反应相对较强,在抗JEV抗体阳性血清中,两者交叉反应较弱。WNV与JEV存在一定交叉反应,但是否有交叉保护作用则需要中和试验等进一步证实。     

Post exposure studies with human diploid cell rabies vaccine and purified chick embryo cell vaccine: comparative serological responses in man

Rabies-neutralising antibody responses to human diploid cell strain rabies vaccine (HDCSV) and purified chick embryo cell vaccine (PCECV) were studied in 125 patients previously exposed to rabid animals having received 3, 5 and 6 doses on days 0, 3, 7, 14, 30 and 90. Antibody response was significantly higher (P less than 0.05) with HDCSV than PCECV in all subjects irrespective of their sex and age group. Three doses on day 0, 3, 7 given for post-exposure rabies prophylaxis to class I patients with a negligible risk elicited antibody titres significantly higher than the minimum protective level required (0.5 I.U./ml); the mean response was greater than 15 I.U./ml in the case of PCECV and greater than 32 I.U./ml in the case of HDCSV. The use of PCECV is cost-effective and suggested for use in developing countries.     

精制Vero细胞狂犬病疫苗的临床观察及免疫学效果 …

目的 目前我国使用的人用狂犬病疫苗生产工艺较落后,致使用后副反应较严重,而国际上Ｖｅｒｏ细胞狂犬病疫苗已研制成功和使用近２０年,不仅免疫效果良好而且副反应很轻。为了改变我国狂犬病疫苗生产工艺的落后和质量较差的状况,而开展此项研究。方法 海南省生物制品研究所和河南省生物技术研究所联合研制的Ｖｅｒｏ细胞狂犬病疫苗获得卫生部批准进行临床观察,该疫苗以ａＧ株适应Ｖｅｒｏ细胞后为生产毒种,转瓶培养、并浓缩适     

Safety, immunogenicity, and efficacy of a Plasmodium falciparum vaccine comprising a circumsporozoite protein repeat region peptide conjugated to Pseudomonas aeruginosa toxin A.

Twenty-one malaria-naive volunteers were immunized with a vaccine consisting of a 22-kDa recombinant peptide (R32LR), derived from the repeat region of Plasmodium falciparum circumsporozoite (CS) protein, covalently coupled to detoxified Pseudomonas aeruginosa toxin A. Nineteen volunteers received a second dose of vaccine at 8 weeks, and eighteen received a third dose at 8 to 12 months. The vaccine was well tolerated, with only one volunteer developing local discomfort and induration at the site of injection which limited function for 48 h. The geometric mean anti-CS immunoglobulin G antibody concentration 2 weeks after the second dose of vaccine was 10.6 micrograms/ml (standard deviation = 3.0 micrograms/ml). Eleven volunteers (52%) developed anti-CS antibody levels of greater than 9.8 micrograms/ml, the level measured in the one volunteer protected against P. falciparum challenge after immunization with the alum-adjuvanted recombinant protein R32tet32 in a prior study. Three separate experimental challenges were conducted with 10 volunteers 2 to 4 weeks after the third dose of vaccine. The four best responders, on the basis of antibody levels (6 to 26 micrograms/ml), were challenged with two infected-mosquito bites, but only one of four immunized volunteers and one of three malaria-naive controls became parasitemic. In a second challenge study using five infected-mosquito bites as the challenge dose, three of three malaria-naive control volunteers and two of three immunized volunteers developed malaria. The third vaccine was apparently completely protected. In the third and last challenge, three of three controls and five of five vaccinees became infected. Sera obtained on the days of challenge inhibited sporozoite invasion of hepatocytes variably in vitro (range, 45 to 90% inhibition), but the degree of inhibition did not correlate with protection. Although antibody against the CS repeat region may protect some individuals against experimental challenge, this protection cannot be predicted from antibody levels by current in vitro assays. The functionality and fine specificity of anti-CS antibody are probably critical determinants.     

Enzyme-linked immunosorbent assay to evaluate the immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans.

A highly sensitive enzyme-linked immunosorbent assay was developed for Klebsiella capsular polysaccharide (CPS) and used to evaluate the immunoglobulin G (IgG) antibody response to a 24-valent CPS vaccine in seven adult volunteers. The median rise in titer to all vaccine antigens in samples from the volunteers was significant (twofold or greater). Significant IgG responses to 11 immunologically related serotypes not included in the vaccine were also noted. The mean cross-reacting IgG titer of 127.2 was only slightly lower than the mean titer of 175.7 to the serotypes in the vaccine (P less than 0.05). The mean 29.9-fold increase in titer to the serotypes in the vaccine was significantly higher than the mean 13.5-fold increase in titer to the additional antigens (P less than 0.001). The difference was partly because of the significantly lower (P less than 0.01) natural antibody titers in the preimmune sera to the serotypes in the vaccine, compared with those to serotypes not included in the vaccine. The selection of vaccine serotypes was based on the frequency of serotype isolation from cases of Klebsiella bacteremia. The above findings, which show low levels of natural antibody to these serotypes, support the hypothesis that anti-CPS antibody is protective against bacteremic disease.     

Evaluation of tests for rabies antibody and analysis of serum responses after administration of three different types of rabies vaccines.

Humoral antibody response to three types of rabies vaccines were assayed by the neutralization (NT), the mixed hemadsorption (MH), and the indirect immunofluorescence (IF) tests. The NT and MH tests were used to detect antibodies combining with antigens at the surface of virions and infected cells, whereas the indirect IF test measured antibodies mainly to the rabies nucleocapsid antigen. After immunization with a human diploid cell vaccine, antibodies were detected by both the NT and the MH test in the 14th- and 30th-day serum samples from each of eight vaccinated persons. There was a good correlation between titers obtained with the two tests in this group of vaccinees. Antibodies elicited by duck embryo and nervous tissue vaccines occurred less frequently and in lower titers. In these groups of vaccinees, 5 of 14 and 5 of 10, respectively, had antibodies detectable by the NT test in the 14th- and 30th-day sera but were negative by the MH test. It is suggested that this was due to the high levels of immunoglobulin M antibodies, which are known to be elicited by daily injections of vaccine. Since antibodies of the immunoglobulin M class are considered to be less important for protection against rabies, the MH test is recommended for immunity determinations. Compared with the NT test, this test also offers the advantage of being technically more convenient because of its capacity for testing numerous sera in a single run. Antibody titers obtained by the indirect IF test in the human diploid cell vaccine group were relatively low. Titers in the duck embryo and nervous tissue vaccine groups were higher but did not correlate with the results of the NT test.     

Vaccination against hepatitis B virus at the Lyon Pasteur Institute. A seven-year evaluation]

Results of immunization against hepatitis B among Pasteur Institute staff members are reported. Prior to immunization, 439 subjects were tested for hepatitis B virus (HBV) markers, including HBs antigen, anti-HBs antibody, and anti-HBc antibody (Ausria, Ausab, Corab assays; Abbott). Forty-seven subjects tested positive for anti-HBs antibody. 317 subjects negative for all the HBs markers studied were given three intramuscular doses of Hevac B (Pasteur vaccins) at one-month intervals. Anti-HBs antibodies were assayed after the third injection with the following results: mean titer, 1,454 mIU/ml, standard deviation, 5,349 mIU/ml, and range, 4 to 41,100 mIU/ml. Anti-HBs titers above 10 mIU/ml were found in 879.4% of subjects. Non-responders and weak responders (anti-HBs titer under 10 mIU/ml) were given a fourth dose of vaccine. Ultimately, after the last (third of fourth) injection 97.6% of subjects had protective antibody titers. No case of HBV infection was seen during the seven-year follow-up period.     

Influences on formation of tetanus antibody after simultaneous injection of tetanus immunoglobulin with tetanus vaccine

The goal of this study was to determine how much the formation of tetanus antibody is influenced after a single injection of tetanus vaccine (Td) and the simultaneous injection of tetanus vaccine with tetanus immunoglobulin (TIG). All of the healthy adult volunteers were divided into two groups: group 1 (Td only) and group 2 (Td plus TIG). Two hundred thirty seven volunteers were enrolled. When the baseline antibody titer, gender and age were adjusted, the geometric mean titers (GMTs) of the tetanus antibody (group 1 vs group 2) was 0.8438 IU/mL vs 0.5684 IU/mL at 4 weeks (P = 0.002), 0.4074 IU/mL vs 0.3217 IU/mL at 6 months (P = 0.072) and 0.3398 IU/mL vs 0.2761 IU/mL at 12 months (P = 0.140) after injection, respectively. The formation of tetanus antibody after tetanus vaccination is not influenced by TIG at the late period and in adults below the age of 50 yr, but there are significant differences between the two groups at the early period of 4 weeks after vaccination and for the patients over 60 yr.     

Prophylactic immunization of humans against rabies by intradermal inoculation of human diploid cell culture vaccine.

The antirabies human diploid cell vaccine produced by 1'Institute Merieux, Lyon, France, was administered intradermally to 35 high-risk volunteers using 0.2-ml amounts and various immunization schedules. Three groups never before vaccinated against rabies developed virus-neutralizing antibodies, the titer of which was dose dependent. A single injection stimulated the formation of antibodies. Four inoculations induced the highest antibody levels and the longest persistence of antibody. The administration of a single intradermal booster inoculation was sufficient, even in the case of low-persisting antibody, to elicit a rapid increase of antibodies to high levels. A primary inoculation course of two injections induced a sufficient antibody level which, in case of exposure, could apparently be rapidly elevated by a 0.2-ml intradermal booster inoculation. Adverse side reactions were observed in 7 of 14 individuals after a 1- or 1.5-year intradermal booster inoculation. We therefore suggest that the intramuscular and subcutaneous routes continue to be used for primary vaccinations and that the highly effective intradermal route be restricted to booster inoculations. This is the first long term study of this vaccine and should be a guideline for the pre-exposure treatment of high-risk personnel.