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PubMedDate not supplied

Glucose tolerance during experimental tetanus toxicity in rabbits.

Tetanus was induced in rabbits by injection of high doses of purified tetanus toxin. After the induction of tetanus, the fasting blood glucose level was significantly elevated in the rabbits with tetanus--blood glucose level being 137.5 mg% compared with 114.8 mg% in controls. The Glucose tolerance showed the expected curve in control rabbits while in the rabbits with tetanus, there was a continuous rise in blood glucose levels even after 3 hours. Histological studies show degranulation of the beta cells of the pancreas in the tetanus rabbits. Thus, the high fasting blood sugar level and the diabetic pattern of Glucose tolerance observed in the tetanus animals are suggestive of reduced insulin production during tetanus, as part of the mechanism involved.

Animals↗
PubMed1990

[High incidence of tetanus in the middle-aged and elderly].

Tetanus is a disease which has a high mortality rate, caused by clostridium tetani. It presents with trismus, difficulty in swallowing, and more ominously difficulty in breathing, or opisthotonus. Included in this retrospective study are 23 cases of tetanus treated in Chang Gung Memorial Hospital between Jan. 1986 and Dec. 1989. Age ranged from 36 to 87, with the highest incidence in the middle-aged and elderly (91% older than 40 years of age). In 20 cases a wound was found as the source of infection, most of which were minor injuries. Of the nine patients who received no medical attention, three received herb drugs. Of the eleven patients who did seek medical attention at the time of injury, four received tetanus toxoid but none of them received human tetanus immunoglobulin. Tetanus is a totally preventable disease. Prevention includes three basic principles: local wound management, active immunization, and passive immunization. When treating injured patients, it is important to recall that many middle-aged and older adults are not adequately immunized against tetanus. Such patients should receive human tetanus immunoglobulin as well as tetanus toxoid.

Adult↗
PubMed1989

Delineation of several DR-restricted tetanus toxin T cell epitopes.

We have characterized five human T cell clones specific for tetanus toxin. The combination of different techniques allowed us to precisely map two T cell epitopes within fragments 830-843 and 1273-1284 of tetanus toxin, as formally demonstrated by the use of corresponding synthetic peptides. The three other T cell clones were specific for regions 2-602, 604-742, and 865-1315 of tetanus toxin, respectively. The five T cell clones were shown to be restricted to HLA-DR Ag. Furthermore, the allele of HLA-DR utilized by the various epitopes has been determined. The use of HLA-DR-transfected L cells as APC directly demonstrated that two epitopes, one of which represented by fragment 1273-1284, were recognized in association with HLA-DRw52a. For the other three T cell epitopes, the data strongly suggested they were recognized in association with HLA-DR5. Finally, a sixth T cell clone was shown to be specific for tetanus toxoid, the vaccinal preparation of tetanus toxin, and not for other tetanus toxin fragments. This indicated that immunization with tetanus toxoid probably elicits a T cell response directed only in part against native tetanus toxin.

Alleles↗
PubMed1988

Protective murine monoclonal antibodies to tetanus toxin.

Monoclonal antibodies against tetanus toxin were generated by fusion of mouse NS-1 myeloma cells with spleen cells from BALB/C mice immunized with tetanus toxoid. Twenty seven hybridomas against tetanus toxin were obtained. Six hybridoma clones, designated as 1A6B12, 1H7D9, 3A8G9, 3A9F2, 3F9H9, 4A6D11 were selected for further studies. All of them were IgG1, k chain and bound specifically to tetanus toxin and toxoid. All six clones were injected intraperitoneally into pristane-primed BALB/C mice. Antibodies with titer up to 10(6) were obtained in the ascites. Results obtained from in vivo neutralization test showed that 1A6B12, 3A8G9, 3F9H9, 4A6D11 mAbs did have neutralizing activities against tetanus toxin. Monoclonal antibody 4A6D11 had the strongest neutralizing activity. 4A6D11 were purified from ascites by DEAE-52 ion exchange chromatography. Comparing to U.S.A. standard antitetanus toxin antiserum, 50 micrograms purified 4A6D11 mAb had 1 international unit neutralizing activity. The purified 4A6D11 mAb was also coupled to cyanogen bromide-activated sepharose to make an affinity column. Pure tetanus toxin can be obtained by passing crude tetanus toxin through this column and eluting the adsorbed toxin with 4M urea. Large scale purified tetanus toxin could be obtained by this method.

Animals↗
PubMed1994

Anti-idiotype antibodies and circulating immune complexes after immunisation with tetanus-toxoid.

OBJECTIVES: To determine if anti-idiotype antibodies and circulating immune complexes in individuals before and after immunisation with tetanus toxoid play a role in the immune response. DESIGN: A study of individuals who were administered a single dose of tetanus toxoid (TT) and who were unimmunized. SETTING: Out patient departments of a large public hospital in Bombay, India. SUBJECTS: Thirty eight individuals pre-immunisation and forty five individuals post-immunisation with tetanus toxoid, tested at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURE: Development of anti-tetanus anti-idiotype antibodies and circulating immune complexes. RESULTS: Pre-immunisation cases did show presence of anti-tetanus antibodies but in lower titres than post-immunisation up to six months, after which there was a reduction. Specific anti-idiotype antibodies were detected in 19 cases. One and three months after immunisation more cases had high titre antibodies and circulating immune complexes, though after six months, there was a fall in anti-tetanus antibody titres. Circulating immune complexes were seen in those samples having anti-idiotype antibodies. CONCLUSIONS: Though a significant rise in anti-tetanus antibody anti-idiotype antibodies, protective levels in mice and circulating immune complexes are seen after immunisation with TT it lasts for six months. When followed up for a period of one year it is observed that in cases having auto anti-idiotype antibodies, the anti-tetanus antibodies are maintained for a longer period.

Antibodies, Anti-Idiotypic↗
PubMed1994

Tetanus in a parenteral drug abuser: report of a case.

Tetanus is an infection caused by Clostridium tetani. In the United States, tetanus remains a significant problem primarily among nonimmunized or inadequately immunized individuals. This article reports a fatal case of tetanus that occurred in a 45-year-old parenteral drug abuser who presented to Harlem Hospital Center with nuchal rigidity, trismus, dysphagia, and spasms of the pectoralis musculature. Multiple cutaneous ulcerations also were observed. Despite aggressive measures that included: endotracheal intubation, administration of human tetanus, hyperimmune globulin, tetanus toxoid, and intravenous penicillin, the patient rapidly deteriorated and manifestations of heightened sympathetic nervous system activity, seizures, and cardiac arrest ensued. The diagnosis of tetanus must be based upon clinical grounds. Clinicians must remain aware of the possibility of tetanus, especially among drug abusers who also are more likely to be evaluated for complications of human immunodeficiency viral infection, which in some cases may mimic tetanus or make the diagnosis more difficult to establish.

Humans↗
PubMed1997

Adjuvanticity of pGPL-Mc and LRS in the immune responses of monkeys to oral immunization with diphtheria and tetanus toxoids.

Experiments were carried out to examine the adjuvanticity of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) or the London rocket seed (LRS) when combined with diphtheria and tetanus toxoids in an oral immunization of the African green monkey. The results showed that none of the monkeys receiving diphtheria and tetanus toxoids combined with 25 mg/kg of pGPL-Mc showed an increase in the the level of diphtheria antitoxin (DA) on the third and sixth weeks following the first and the second immunizations. One monkey from this group responded with increased seroneutralizing antibodies 3 weeks after the third feeding. On the other hand, one monkey, 3 weeks after the first immunization, and three monkeys, 3 weeks after the second and third oral vaccinations, showed an increase in specific anti-diphtheria antibody responses when the toxoids were combined with 25 mg/kg of LRS. The anti-diphtheria antitoxin responses of monkeys receiving diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc or 50 mg/kg of LRS were significantly enhanced compared to the groups administered 25 mg/kg of the two adjuvants. The increase was observed in four out of five pGPL-Mc administered and in three out of five LRS-receiving monkeys. The results show that pGPL-Mc induced the highest titres of anti-diphtheria antitoxin compared to LRS, whereas the level of anti-diphtheria antitoxin titre of the two monkeys receiving the toxoids alone was less than 0.1 i.u./ml of serum throughout the experiment. According to the statistical analyses, no significant differences were recorded between the diphtheria antitoxin responses of monkeys following the first, second or third administration of LRS-adjuvated diphtheria and tetanus toxoids. However, a significant difference (P < or = 0.05) was observed in the diphtheria antitoxin response between the first and the second immunization of monkeys administered with toxoids adjuvated with 50 mg/kg of pGPL-Mc. The tetanus antitoxin responses of all monkeys were less than 0.1 i.u. of antitoxin per millilitre of serum throughout the study, which is considered not to be protective. However, we have recorded an anti-tetanus antitoxin titre of more than 0.2 i.u./ml of serum in one monkey that received diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc.

Adjuvants, Immunologic↗
PubMed2000

Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children.

The effects of vitamin A and vitamin E supplementation on the IgG response to tetanus toxoid after primary immunization were evaluated in a prospective, randomized controlled clinical trial involving 89 healthy infants with normal serum vitamin A and E levels at 2 months of age. Before the first dose of DPT vaccine, the infants were randomly enrolled into four different study groups [Group I (n=24): 30,000 IU vitamin A for 3 days just after each three doses of primary vaccination, Group II (n=21): 150 mg oral vitamin E for only 1 day after the injections for primary immunization, Group III (n=21): vitamins A and E together in the same order, Group IV (n=23) no vitamin after DPT vaccines]. Serum tetanus antitoxin (IgG) titres were measured three times; initially at 2 months of age before the first dose of DPT, secondly at 5 months of age 1 month after primary immunization and thirdly at 16-18 months of age before the booster dose of DPT. Before the first dose of the DPT vaccine, 1 month after the third DPT injection and at 16-18 months before the booster dose of DPT, there was no significant difference in serum tetanus antitoxin levels between these four groups. A significant increase was observed in all the groups when serum tetanus antitoxin levels before (2 months) and after (5 months) primary immunization were compared. In addition, serum antibody levels against tetanus significantly decreased in the four groups before booster vaccination. Before the beginning of primary immunization, 15 infants (16.8%) had serum tetanus antitoxins (IgG) below protective level. After three doses of DPT, all the infants had protective antitoxin levels. At 16-18 months of age before booster dose, four infants (10%) also had serum tetanus antitoxins (IgG) below the protective level. No side-effects were observed except bulging fontanelle in two infants in Group I.

Antibody Formation↗
PubMed1984

Analysis of the immune response to papain digestion products of tetanus toxin.

Tetanus toxin was degraded by papain and the previously characterized Fragment B and Fragment C were isolated. The induction of protective immunity against tetanus toxin was subsequently investigated in two animal models using Fragment B and Fragment C, as well as conventional tetanus toxoid for comparison. In guinea pigs, Fragment B showed an immunizing potency similar to that recorded for an equal amount of tetanus toxoid, whereas Fragment C was considerably less efficient, on an equal weight basis. In contrast, mice immunized with Fragment C reached a protection level similar to that achieved after immunization with the complete tetanus toxoid antigen. In both animal models, Fragments B and C acted in a synergistic fashion when injected together. Analysis of sera from guinea pigs using ELISA, after administration of a low dose of tetanus immunogen corroborated these results. The data indicate that antigenic determinants in distinct regions of the toxin molecule independently may induce antibodies neutralizing the lethal action of tetanus toxin. The immune response to the complete toxoid antigen may be subject to influence by intramolecular competition between antigenic determinants. The immunogenicity of the fragments as measured by the protection rate after active immunization may depend upon the animal species used.

Animals↗
PubMed2001

Age- and sex-determined differences in the establishment of tetanus antitoxin production in guinea-pigs.

For lack of relevant data of the literature, the tetanus immunisation results obtained in the two sexes were compared in an animal model. Complete immunisation series of weaned, adult and aged guinea-pigs (20-25 animals/group) were performed with aluminium phosphate (AlPO4) adsorbed purified tetanus toxoid (PTAP) as well as with typhoid-tetanus vaccine (TY-TE) containing lipopolysaccharide (LPS). Both vaccines contained 5.0 Lf (limes flocculans, Ramon) per single dose of tetanus toxoid, purity degree: 1500 Lf/mg protein nitrogen (PN). Tetanus antitoxin titres (TAT) were measured after the first shot, and subsequently before and after booster. Compared to TAT of male animals, significantly lower titres were found in female animals after basic immunisation with PTAP in all the three age groups: 1.03 vs. 0.57, 8.75 vs. 5.64, and 0.27 vs. 0.15 IU (international units, related to the Copenhagen International Standard) per ml (sex-chromosome-dependent differences?), as well as in adult animals immunised with TY-TE, before booster: 0.07 vs. 0.02 IU/ml (hormone-dependent differences?). In the latter case the TAT results after booster were 14.49 vs. 12.89 IU/ml. Thus, the lower female prebooster titres were counterbalanced by a quick and effective increase of titres following booster. These results are in accordance with our previous observations in humans (Réthy and Réthy, 1986). From our observations with tetanus immunisation series on guinea-pigs it can be concluded that TAT may be influenced by the effects of sex chromosomes as well as of sexual hormones. During active anti-tetanus immunisation with LPS-containing vaccine (TY-TE) the lower adult female prebooster titres are presumably counterbalanced by the better functionality of the female immune memory.

Adjuvants, Immunologic↗
PubMed1998

An antibody induction method in mice for the potency assays of diphtheria and tetanus components in combined vaccines.

Eleven batches of Adsorbed Diphtheria-Tetanus (DT) vaccines and thirteen batches of Adsorbed Diphtheria-Pertussis-Tetanus (DTP) vaccines were tested for the potency of diphtheria and tetanus components by an Antibody Induction Method (AIM) developed in mice. The potency results obtained were found comparable and did not show any statistically significant difference with those obtained by WHO recommended lethal challenge tests for diphtheria in guinea pigs and for tetanus in mice. AIM in mice is more economical as both diphtheria and tetanus components of combined vaccine can be tested in the same experiment and the procedure also eliminates the use of guinea pigs required in the lethal challenge/conventional tests. The data obtained while testing tetanus component by the conventional antibody induction (IP) method in guinea pigs suggests that minimum requirements laid down in i.p. is too low which may be fixed as at least 3 out of 9 guinea pig sera and should contain > or = 4 units of tetanus antitoxin per ml.

Animals↗
PubMed1985

Tetanus and the aged.

Tetanus is primarily a disease of the aged. Even though the overall number of cases of tetanus has decreased since 1955, the number of cases of tetanus in people 50 years of age and older has remained constant. The national Center for Disease Control attributes the cases of tetanus in the aged to inadequate immunization levels. Tetanus is preventable and, theoretically, could be eradicated if the population was at an adequate immunization level. There are many reasons why older people are not adequately immunized. These reasons may include the inability to get to a health care facility due to physical disability or lack of transportation, ignorance of the importance of seeking health care for minor injuries, financial constraints and a knowledge deficit on the part of health care providers regarding the immunization needs of the aged. Health care providers can prevent tetanus in the aged through vigilance. All aged clients should be routinely assessed and immunizations updated as necessary. Tetanus will never be eliminated until universal active immunization has been achieved.

Aged↗
PubMed1979

Immunization aginast tetanus with aluminium free-versus aluminium contain triple vaccine.

In order to discover if elimination of aluminium from the very effective triple vaccine gives an unsatisfactory immunity against tetanus, the following investigation has been performed. 47 children were immunized in 1968 and 1969 during the first year of life with 3 injections of aluminium free triple vaccine given with an interval of 4--6 weeks. The vaccine contained 10 Lf tetanus toxoid per dose. 8 years later, during 1976 and 1977, they were given boosters containing aluminium adsorbed Td with 4 Lf tetanus toxoid. The above mentioned group was compared with 29 children immunized in the 1950's in the same way but with aluminium adsorbed triple vaccine (13--19 Lf tetanus toxoid per dose). The booster with DT given 6 to 7 years later contained 8 Lf aluminium adsorbed tetanus toxoid. The serum content of tetanus antitoxin was determined before and after the booster. The result showed that the tetanus immunity was very satisfactory even though the basic immunization was performed with aluminium free triple vaccine.

Aluminum↗
PubMed1977

Neutralization of tetanus toxin by human and rabbit immunoglobulin classes and subunits.

This investigation found that the human antibody class of importance in neutralizing tetanus toxin in mice was IgG, and that toxin neutralization was retained by the F(ab')2 and Fab' subunits of the human IgG class. Although human IgM and IgA classes appeared to neutralize tetanus toxin at very low levels, evidence was obtained that this neutralization was probably due to IgG contamination. Human Fabmu isolated from the IgM class did not neutralize tetanus toxin. Human antibodies of the IgG, IgM and IgA classes reacted with tetanus toxoid in the indirect haemagglutination (HA) test with IgG giving the highest HA titre. Rabbit antibodies of the IgG class also neutralized tetanus toxin, with neutralization being retained by the F(ab')2 and Fab' subunits of the rabbit IgG class. Absorption of several rabbit antisera to tetanus toxoid with goat-antirabbit Fc which is specific for absorption of IgG from antiserum, rendered them incapable of neutralizing tetanus toxin.

Animals↗
PubMed1996

Use of in vitro Vero cell assay and ELISA in the United States potency test of vaccines containing adsorbed diphtheria and tetanus toxoids.

Current United States (US) regulations for potency testing of vaccines containing adsorbed diphtheria and tetanus toxoids require in vivo toxin neutralization (TN) tests on the pooled sera of immunized guinea pigs. To reduce the number of animals required for testing, two in vitro tests have been evaluated, the Vero cell assay for diphtheria antitoxin and ELISA for IgG antibody to tetanus toxin; these have been correlated with in vivo TN tests. In the Vero cell method, diphtheria antitoxin titres of the guinea pig sera, obtained four weeks after immunization as per US potency requirements, were markedly dependent on the toxin dose level used in the assay. A toxin dose level termed the Lcd/1 dose (limit of cytopathic dose at a IU/ml) for Vero cells gave comparable estimates of antitoxin activity to the in vivo TN test performed at L+/1 dose of toxin. When lower dose levels of toxin were used in the Vero cells (Lcd/10 to Lcd/1000), diphtheria antitoxin levels in four weeks guinea pig sera were two to 11.7 times lower than with the Lcd/1 dose level. The most likely reason for these differences is that guinea pig sera a 4 weeks are of lower avidity than the equine antitoxin standard. Antibodies of low avidity bind antigen less well at low reactant concentrations. Therefore, to obtain similar estimates of diphtheria antitoxin in the Vero cell method and in vivo TN test, the use of toxin dose for the Vero cell method similar to that for the in vivo TN test is suggested. Another alternative, in which any dose of toxin may be used for the Vero cell method, is the use of a reference guinea pig serum (calibrated in IU/ml by the in vivo TN test at L+/1 level of toxin) that has similar avidity or similar immunization status as the test sera (i.e. 4 week serum). IgG antibodies to tetanus toxin in guinea pig sera were found early in the course of immunization when tetanus antitoxin could not be detected by TN test. Tetanus toxin IgG antibody levels of guinea pig sera calculated in IU/ml against an ELISA guinea pig reference serum (calibrated in IU/ml by TN test) depended upon the immunization status of the animals. To obtain similar estimates of tetanus antibodies in IU/ml by TN and ELISA, the ELISA reference guinea pig serum should have similar immunization status (and presumably similar avidity) as the test serum (i.e. six week serum). We propose that the Vero cell method and ELISA deserve further evaluation to determine whether they can replace in vivo TN tests for titration of diphtheria and tetanus antitoxins in the US potency test.

Animal Testing Alternatives↗
PubMed1981

Enhancement and diminution of mechanical tension evoked by staircase and by tetanus in rat muscle.

1. Potentiation of the isometric twitch tension was compared during and after the staircase and after tetanic stimuli in the fast-twitch extensor digitorum longus muscle of adult Lewis rats at 37-38 degrees C.2. With up to 250 stimuli the potentiation rose with an increase in both the frequency and number of stimuli in the staircase (2-5/sec) and the tetanus (100-167/sec). After a tetanus of 375 stimuli (125/sec) the potentiation was smaller. The potentiation 2 sec after a tetanus of 250 stimuli (167/sec) was + 132 +/- 5% (n = 21, s.e. of mean) which was greater (P < 0.001) than at the 250th stimulus at 5/sec, +92+/-3% (n = 21, s.e. of mean).3. After the staircase the decay of potentiation was initially slow and later more rapid. This was taken to indicate both the recovery of a process that diminished twitch tension and the decay of a process causing potentiation. After 250 stimuli (5/sec) the rate of decay of the processes causing diminution and potentiation had time constants of 34.5 +/- 3.8 sec (n = 18, s.e. of mean) and 102.2 +/- 6.6 sec (n = 20, s.e. of mean) respectively. Compared with the potentiation, the process causing diminution became relatively more pronounced the greater the frequency of stimuli.4. The decay of post-tetanic potentiation showed an initial rapid and a later slower phase of decay. After a tetanus of 250 stimuli (167/sec) the rates of decay had time constants of 5.7 +/- 0.8 sec (n = 16, s.e. of mean) and 113.5 +/- 8.7 sec (n = 19, s.e. of mean) respectively.5. Compared with the unpotentiated response the time course of the twitch was shortened initially in the staircase and when the post-tetanic potentiation was low. The contraction time was then increasingly prolonged the greater the potentiation and the greater the number of stimuli in the staircase and in the tetanus. The half-relaxation time was the more prolonged the greater the number of stimuli.6. Potentiation can be described in terms of a two-compartment model of processes which show saturation. Both compartments were activated in a tetanus whereas only the compartment with a slow rate of decay was activated in the staircase. It is speculated that the two compartments are related to the excitation-contraction coupling. The process that caused diminution of twitch tension during the staircase may be due to fatigue. It is suggested that the energy consumption in 250 twitches is about 10 times greater than in a tetanus of 250 stimuli which may explain the presence of fatigue after the staircase whereas it was absent after the tetanus.

Action Potentials↗
PubMed1997

Effects of electrically induced fatigue on the twitch and tetanus of paralyzed soleus muscle in humans.

We analyzed the twitch and summated torque (tetanus) during repetitive activation and recovery of the human soleus muscle in individuals with spinal cord injury. Thirteen individuals with complete paralysis (9 chronic, 4 acute) had the tibial nerve activated every 1,500 ms with a 20-Hz train (7 stimuli) for 300 ms and a single pulse at 1,100 ms. The stimulation protocol lasted 3 min and included 120 twitches and 120 tetani. Minimal changes were found for the acute group. The chronic group showed a significant reduction in the torque and a significant slowing of the contractile speeds of both the twitch and tetanus. The decrease in the peak twitch torque was significantly greater than the decrease in the peak tetanus torque early during the fatigue protocol for the chronic group. The twitch time to peak and half relaxation time were prolonged during fatigue, which was associated with improved fusion of the tetanus torque. At the end of the fatigue protocol, the decrease in the peak twitch torque was not significantly different from the decrease in the peak tetanus torque. After 5 min of rest, the contractile speeds recovered causing the tetanus to become unfused, but the tetanus torque became less depressed than the twitch torque. The differential responses for the twitch and the tetanus suggest an interplay between optimal fusion created from contractile speed slowing and excitation contraction coupling compromise. These issues make the optimal design of functional electrical stimulation systems a formidable task.

Acute Disease↗
PubMed1999

Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine.

A guinea pig model to assess the immunogenicity of a combination vaccine containing diphtheria, tetanus and acellular pertussis (DTaP) vaccine and Haemophilus influenzae type b (Hib) capsular polysaccharide conjugated to tetanus toxoid (HibT) was evaluated comparatively with the mouse immunogenicity test to study the effect of combining these antigens on the immunogenicity of various components. The immunogenicity test in mice was performed by subcutaneous injection of groups of 10 animals twice at an interval of four weeks with 1/10 of a single human dose of various formulations of combination vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks and IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals injected subcutaneously twice at an interval of six weeks with 1.5 times the single human dose of various formulations. The animals were bled at 4, 6 and 8 weeks and serum samples were tested for antibodies to various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus and diphtheria components was assessed as per the US Food and Drug Administration's regulations. Aluminium phosphate (AIPO(4)) adsorbed HibT vaccine or HibT as a combination with AIPO(4)adsorbed DTaP vaccine showed significant increases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In general, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine elicited significantly lower IgG antibodies to pertussis toxin and filamentous haemagglutinin than DTaP vaccine alone, particularly after first injection. Mice showed similar Hib antibody responses for the combination and HibT alone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount of HibT and/or tetanus toxoid in the combination formulations reduced this suppression of Hib antibody response in guinea pigs. Suppression of Hib antibody response in combination vaccines has also been reported from recent clinical trials. Based on the results from this study, it appears that the guinea pig model may be able to predict the human response to various components of combination vaccines.

Animals↗