Decline In Antibody Titers Research Articles

Psychosocial Factors and the Response to Influenza Vaccination in Older Adults

We examined the influence of psychological state (depression, negative affect, perceived stress) and social support on pre- and post-vaccination response to influenza vaccine. Venous blood was drawn from 37 nursing home residents before and following injection of the trivalent influenza vaccine (comprised of the New Caledonia (NC), Hong Kong (HK), and Panama (Pan) strains of flu). The Geriatric Depression Scale, Perceived Stress Scale, Positive and Negative Affect Schedule, and Multidimensional Scale of Perceived Social Support were completed following the initial blood draw. Social support and perceived stress were correlated with pre-vaccine antibody responses to two of the three vaccine components (HK and NC). Social support was negatively correlated with both pre- and post-vaccine titers to Pan. Depression, positive affect, and negative affect were not related to vaccine response. Perceived stress and social support influence the rate of decline of antibody titers to previous exposures to some strains of influenza occurring either naturally or via deliberate vaccination.

Usefulness of serological IgG antibody determinations for confirming eradication of Helicobacter pylori infection

OBJECTIVE: Prior studies have suggested that IgG antibody titers may be useful to confirm successful treatment of Helicobacter pylori ( H. pylori) infection. However, the diagnostic value of decreasing IgG titers is limited by the necessity to perform pre and posttreatment tests in parallel which requires stored sera. Our objective was to assess the accuracy of IgG antibody titers using the HM-CAP IgG EIA kit (Enteric Products) in monitoring treatment of H. pylori infection and to compare the relative accuracy of parallel versus serial determinations. METHODS: The 14C urea breath test (UBT) was used to confirm H. pylori infection in 83 dyspeptic patients and eradication of the organism at 4 wk and 6 months posttreatment. IgG titers pretherapy and 6 months posttherapy were determined either serially (separate EIA plates) or in parallel (same EIA plate), and the relative percent decline in antibody titer was calculated. RESULTS: When a decline of ≥25% at 6 months was used as the cut-off for H. pylori eradication, mean sensitivities of serial and parallel determinations were 87.5% and 86.8%, respectively, and mean specificities of both were 100%. In 68 of 75 patients in whom the organism was eradicated, the mean decrease in IgG titer at 6 months was 41.1% for serial determinations and 41.5% for parallel determinations. CONCLUSIONS: Serial or parallel IgG titers offer equivalent diagnostic accuracy for confirming H. pylori eradication after therapy. A ≥25% decline in titer 6 months after therapy is a sensitive and specific marker for eradication of the infection. Serial evaluation of IgG titers does not require serum storage, and is a cost-effective and accurate alternative to the UBT or endoscopy-based methods.

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Short-Term Follow-Up by Serology of Patients Given Antibiotic Treatment for Helicobacter pylori Infection

Helicobacter pylori serology and in particular enzyme-linked immunosorbent assays for the measurement of immunoglobulin G (IgG) antibody titers form an accurate means of diagnosing H. pylori infection in patients before treatment. H. pylori serology is of limited value in monitoring treatment because of the slow decline in antibody titers. In the present study we aimed to measure the most suitable moment after antibiotic treatment at which serology should be used to monitor treatment. Sixty-four patients who had nonulcer dyspepsia and H. pylori infection and who underwent upper gastrointestinal endoscopy because of persistent dyspeptic symptoms were included in the study. H. pylori cure was confirmed by histology and culture 5 weeks after the completion of the antibiotic treatment. Serological examination was performed before therapy and at 5 weeks, 10 weeks, and 1 year after the completion of antibiotic treatment. Diagnostic performance was assessed by receiver-operating characteristic analysis. The areas under the receiver-operating characteristic curves of the H. pylori antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment were 0.53 (95% confidence interval [CI], 0.36 to 0.69), 0.60 (95% CI, 0.43 to 0.76), and 0.78 (95% CI, 0.63 to 0.93), respectively. The areas under the receiver-operating characteristic curves of the changes in H. pylori IgG antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment in comparison with the pretreatment titers were 0.85 (95% CI, 0.72 to 0.97), 0.96 (95% CI, 0.89 to 1.0), and 1.0 (95% CI, not estimable), respectively. We conclude that serology forms a useful means of monitoring treatment in patients with nonulcer dyspepsia and H. pylori infection as early as 10 weeks and maybe even sooner after the completion of treatment for the infection.

Long-term high immune response to diphtheria toxoid in rodents with diphtheria toxoid conjugated to dextran as a single contact point delivery system

Cross-linked dextran beads were used as a carrier for development of a ‘single-contact’ vaccine delivery system. Diphtheria toxoid (DT) was covalently coupled to dextran beads (DEX-DT conjugate). The conjugate was immunoreactive with antibodies raised against native DT. Immunization of rats with DEX-DT conjugate generated on average 24 times higher antibody titres against diphtheria toxoid than immunization with the conventional DT absorbed on alum. The immune response was sustained for 9 months, with gradual decline of antibody titres thereafter. Significant antibody titres were measurable in rats after 1 year of immunization. DEX-DT had neither acute nor long-term adverse effects on the health of animals, as evidenced by local reactions, general behaviour, food intake, body weight gain and survival compared with controls.

Paraneoplastic Retinopathy

We present the case of a 74-year-old man with rapidly progressive bilateral visual loss, optic disc pallor, retinal arteriolar attenuation, and an abnormal electroretinogram with a 90% reduction in cone function and a 50% reduction in rod function. He was examined for a suspected cancer-associated retinopathy (CAR). Although he was found not to have expressed the previously reported 23-kd CAR antibody, high titers were found of an antibody to a 60-kd retinal protein, which as yet remains unidentified. An initial clinical search for an underlying cancer was unsuccessful, but 2 months later a mediastinal mass was found on chest x-rays, and biopsy confirmed a diagnosis of small-cell lung carcinoma. Combined therapy with oral corticosteroids and plasmapheresis resulted in a recovery of vision from counting fingers to 20/200 in the right eye and 20/40 to 20/25 in the left eye. Conventional chemotherapeutic management of the small-cell lung carcinoma was instituted, and the modest visual recovery was maintained. The visual improvement as well as lung tumor regression were accompanied by a decline in antibody titers from 1:2,000 pretreatment to 1:200 during the course of therapy. The absence of reactivity with the previously described 23-kd retinal antigen of the CAR syndrome does not exclude the diagnosis of paraneoplastic retinopathy in patients fitting the clinical profile of this disease.

Study of employees with anhydride-induced respiratory disease after removal from exposure.

The purpose of this study was to determine clinical and immunologic status of hexahydrophthalic anhydride (HHPA) employees who have had immunologic respiratory disease and who have been removed from exposure for at least 1 year. In a retrospective study, 16 consecutive employees with HHPA-induced immunologic respiratory disease who had been removed from exposure for more than 1 year were evaluated. Eleven had asthma, allergic rhinitis, or both; five had hemorrhagic rhinitis. Respiratory symptoms were obtained by physician-administered questionnaire. Physical examination, spirometry, and chest film were obtained. Antibody against HHPA conjugated to human serum albumin (HHP-HSA) was determined by enzyme-linked immunosorbant assay. Symptoms, signs, and pulmonary functions were normalized in all employees. There was a decline in antibody titers for both IgE and IgG against HHP-HSA. There were no chest film findings attributable to HHPA. In this group, there appeared to be no evidence of permanent anatomic sequelae after removal from exposure for at least 1 year. Specific antibody was still present, but titers were lower at follow-up than at presentation for a substantial proportion of the sample.

Antifertility effects of porcine zona pellucida-3 immunization using permissible adjuvants in female bonnet monkeys (Macaca radiata): reversibility, effect on follicular development and hormonal profiles.

Female bonnet monkeys Macaca radiata (n = 8, four per group) were immunized with purified 55 kDa glycoprotein from porcine zona pellucida (ZP3) and ZP3 conjugated to the beta subunit of human chorionic gonadotrophin (beta hCG) using adjuvants permissible for human use (alum, muramyl dipeptide and sodium phthalyl derivative of lipopolysaccharide). The animals were monitored for anti-ZP3 antibody titres, biweekly progesterone concentrations, menstrual cyclicity and status of fertility. All the animals generated a good anti-ZP3 antibody response, continued to have ovulatory cycles, remained infertile in the presence of high anti-ZP3 antibody titres and showed no disturbance in cyclicity (except summer amenorrhoea). Examinations by laparoscope showed normal ovaries with developing follicles or corpora lutea on the surface. Fifty per cent of the animals conceived after a decline in antibody titres. Ovaries of animals that failed to regain fertility were examined for changes in morphology at times when anti-ZP3 antibody titres in the circulation were low and following a booster when titres were high. None of the ovaries showed any sign of inflammation or lymphocytic infiltration. Follicles at different stages of development were seen in all of the ovaries. No significant reduction in the number of follicles, except in one monkey (MRA 178), was observed. There was no increase in the numbers of atretic or degenerating follicles. The results showed that ZP3 immunization with permissible adjuvants could be used for immunocontraception without obvious ovarian changes.

High Frequency of B Cells Capable of Producing Anti-Thyrotropin Receptor Antibodies in Patients with Graves' Disease

Hyperthyroidism in Graves' disease (GD) is mediated by antibodies to the thyrotropin receptor (TSHr). Patients that go into remission show a decline in antibody titer. However, upon cessation of treatment with anti-thyroid drugs a significant proportion of patients relapse and TSHr antibodies (TSHrAb) are present in their circulation. This suggests that B cells capable of producing TSHrAb persist despite treatment. To determine the frequency of these cells, B cells from six patients with GD and four healthy controls were infected with Epstein-Barr virus and cultured in 96-well plates at varying cell concentrations. A higher frequency of B cells capable of producing TSHrAbs was detected in patients with GD, relative to normal controls. For example, at 2 × 10 5 cells per well, 100% of wells containing cells from either patients with GD or controls were positive for immunoglobulin (Ig) production. In contrast, 27% of the wells containing cells from Graves' patients, and only 3% from controls, were positive for TSHrAb. Higher titers of TSHrAbs were produced in cultures containing lymphocytes from patients with GD and were predominantly of IgG isotype. All patients with GD who had high thyrotropin binding inhibitory immunoglobulins also had higher frequencies of TSHr-specific B cells. These findings show that TSHrAb-producing B cells are present at a higher frequency in the peripheral circulation of patients with GD.

Long-term contraceptive efficacy of vaccine of ovine follicle-stimulating hormone in male bonnet monkeys (Macaca radiata).

A group of ten healthy fertile adult male bonnet monkeys were actively immunized using procedures acceptable for human use with pure follicle-stimulating hormone (oFSH) isolated from sheep pituitaries. The vaccine elicited an immunogenic response in all ten monkeys; the antibody-binding capacity, determined by Scatchard analysis, varied from 3 to 18 micrograms oFSH ml-1, the binding affinity ranging from 0.13 to 2.0 x 10(10) mol-1. A substantial population of antibodies against oFSH crossreacted with 125I-labelled human (h) FSH, used here as a representative ligand of primate FSH. The bioneutralization activity of the antisera assessed by a specific bioassay in vitro, when the antibody titre was high, was 6.9 +/- 0.18 micrograms hFSH ml-1. Immunization for 4.7-5.7 years did not affect the health and libido of the animals. Concentration of testosterone in serum remained normal throughout the study, but, within 150 days of immunization, there was a marked decrease (75-100%) in the number of spermatozoa in seminal ejaculates. Oligospermic status interspersed with azoospermia was maintained by periodic boosting. The fertility of these animals was monitored between 6 months and 2 years after primary immunization. All the ten animals proved infertile in repeated mating experiments with females of proven fertility. After stopping booster injections, nine of ten animals regained fertility, but the time taken for this depended upon the rate of decline of antibody titres. Re-boosting these monkeys with 100 micrograms oFSH after confirming that recovery had occurred revealed prompt increases in antibody titres followed once again by onset of oligo-azoospermia and infertility, underscoring the specificity of immunization effect. The immunized monkeys, apart from being acutely oligospermic, ejaculated spermatozoa that were markedly deficient in key acrosomal enzymes, such as acrosin and hyaluronidase, and motility as well as in their ability to penetrate a gel in vitro, suggesting that the infertility observed was due to gross reductions in the numbers of spermatozoa that could effectively interact with the oocyte and cause successful fertilization.

Response to Trivalent Oral Poliovirus Vaccine with and without Immune Serum Globulin in Young Adults in Israel in 1988

Fifteen cases of type 1 paralytic poliomyelitis occurred in August 1988, mainly among young adults in the Jewish population of Israel, where vaccine coverage exceeds 90%. The military forces, as a precaution against further spread of the virus, vaccinated all recruits in late September. They received oral poliovirus vaccine (OPV) simultaneously with prophylactic immune serum globulin (ISG) to protect against hepatitis A virus infection. Since it is generally not recommended to administer live vaccines simultaneously with ISG, the serologic response to OPV given at the same time as ISG was compared with the response when OPV was given alone; specimens were also available from a control group receiving ISG alone. No effect of ISG on the antibody response to OPV was found, and thus there appears to be no contraindication to giving OPV at the same time as injecting pooled ISG--particularly relevant for travelers to areas endemic for both diseases, who have to leave at short notice. Of recruits 18-19 years of age, 21% lacked antibodies to type 1 poliovirus, suggesting either a decline in antibody titers with age or a lack of vaccine potency during earlier years. After the booster, only 2% lacked type 1 antibody, and the geometric mean titer increased from 1:16 to 1:698.

Flow Rate Dependence of in vitro Removal of Anti-A and Anti-B Antibodies by Immunoadsorbents with Synthetic Oligosaccharides Representing Blood Group Substances

In vitro removal of anti-A and anti-B antibodies by immunoadsorbents with synthetic oligosaccharide structures representing blood group substances have been studied under controlled and simulated extracorporeal perfusion conditions at different flow rates ranging from 20 to 160 mL/min. There is a gradual decline in antibody titers in the plasma, as it relates to the antibody binding capacity and efficiency of the immunoadsorbents, both as a function of time and plasma volume at any of the flow rates employed. Approximately the same maximal binding capacity is achieved in about 4 hours of perfusion regardless of the flow rate, whereas increased number of plasma volumes are required at higher flow rates to compensate for the appropriate residence times needed in the column to utilize the same capacity. The perfusion time alone appears to be a critical factor which via the flow rate determines the residence time between the plasma and the immobilized hapten in the column. Also, the optimal flow rate at which maximum binding capacity of the immunoadsorbent may be utilized efficiently appears to fall within a range of the flow rate. The factors determining this range and the efficiency of the immunoadsorbents under dynamic conditions are discussed. The results obtained under the controlled conditions and the discussions that follow are expected to be generally useful, at least, as approximate clinical guidelines, for selective removal of specific substances by extracorporeal perfusion techniques utilizing therapeutic intervention with immunoadsorbents in this important area of medical therapy.

Spontaneous and post-treatment antibody kinetics in late Lyme borreliosis

The two principal methods involved in the serodiagnosis of Lyme borreliosis are the indirect immunofluorescence assay (IFA) and the indirect quantitative enzyme immunoassay (EIA). There is little data on their suitability for the follow-up of patients after therapy or their ability to define a cure. While IgM titers may be helpful indicators of active disease in the early stages, they are missed in most cases of late stage borreliosis. Patients included in a prospective randomized trial that compared cefotaxime against penicillin for the treatment of late Lyme borreliosis were serologically followed up over a twelve month period by the determination of IgG antibody titers, by IFA, EIA and Western blot. A significant decline of antibody titers in comparison with a control group of untreated patients was observed with the IFA, but not with the EIA, except for patients with Lyme arthritis. IFA titers declined by fourfold in the first three months after the onset of therapy, reaching a base-line of persistent antibody concentration. EIA titers, revealed only a small drop. Neither of the antibody tests proved to be suitable for indicating cure.

Long-term Immunogenicity of a Plasma-Derived Hepatitis B Vaccine in HIV Seropositive and HIV Seronegative Hemophiliacs

Short-term studies indicate that hepatitis B vaccines are safe and satisfactorily immunogenic in hemophiliacs. The duration of immunity in these immunocompromised patients, however, is not known. To determine this, we studied 78 hemophiliacs prospectively 2, 3, and 4 years after the initial vaccination with a plasma-derived vaccine given as three monthly injections followed by a fourth booster injection at month 14. The duration of immunity clearly depended on whether the patients were infected with the human immunodeficiency virus (HIV). In HIV seronegative hemophiliacs (n = 67), there was a progressive decline in titers of antibody to the hepatitis B surface antigen (anti-HBs), but antibody was still detectable 4 years later in all of them. From the curves of decline of antibody titers, it appears that there is no need to revaccinate patients for at least 5 to 6 years. The HIV seropositive hemophiliacs (n = 11) not only started from much lower anti-HBs titers, but 5 of 11 lost anti-HBs. None of the 45 patients treated with concentrates during the postvaccination period developed serologic signs of hepatitis B, even though 6 of them had come into contact with live or inactivated hepatitis B virus as shown by the occurrence of spontaneous anamnestic antibody responses. This vaccine and schedule of vaccination afford a prolonged duration of immunity in HIV seronegative hemophiliacs, but HIV seropositive hemophiliacs have a risk of losing immunity early.

The epidemiology of the human rabies threat in the grand duchy of Luxembourg

Epidemiological data were recorded and blood samples were obtained from a group of 297 individuals from Luxembourg who had been in contact with rabies-infected or -suspected animals from 1979 to 1985, and who had been vaccinated with a complete course of HDCS rabies vaccine. The majority of the subjects were farmers aged between 30 and 59. The most frequent source of infection was cattle, followed by foxes, sheep and cats. Dogs were in the fifth position only, probably as a direct result of obligatory vaccination of dogs in Luxembourg. Animal rabies was proven in 253 of the 297 cases; in 35 cases, rabies diagnosis was not confirmed, and in 9 cases the animals escaped. Concerning the mode of contact, most people (86%) reported having had contact which caused no skin lesions. Contact with skin lesion, i.e. by biting, scratching or scraping, was only reported in connection with dogs, cats and wild animals, whereas with cattle and other farm animals, contact was mostly without skin lesion. The hand was the part of the body (85%) most frequently involved. Sera were tested by an enzyme immunoassay for rabies antibodies. The results were unsatisfactory: 21.5% of the cases had no demonstrable antibodies and 15.2% had antibodies in low titre. No decline in antibody titre was found according to the time interval after vaccination. Therefore, the enzyme immunoassay does not appear to be optimal to determine long-term immunity.

Immunology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. An update.

Recent advances in the understanding of the pathogenesis of infection with human immunodeficiency virus (HIV) stems from the demonstration that the membrane glycoprotein, CD4, is the cellular receptor for HIV. This glycoprotein is found mainly on the surface of a major subpopulation of T lymphocytes and also on macrophages, natural killer cells, some B lymphocytes, and neuronal cells. Cells infected with HIV may be destroyed or have their normal function impaired. Host immune responses to HIV are poor and are not sustained. Neutralizing antibody often is not produced, or HIV may escape from normal immunosuppressive mechanisms through the process of rapid antigenic variation. Factors and markers that may be important in the outcome or that may predict progression of HIV infection are genetic (Gc type), environmental (nutritional status or intercurrent sexually transmitted diseases sustained by the host), and immunologic (rate of decline in number and impairment of function of CD4 lymphocytes and of decline in antibody titers to HIV core protein, p24). A recombinant vaccine will probably be developed for testing in future clinical trials.

Serological tests for blastomycosis: assessments during a large point-source outbreak in Wisconsin.

Enzyme immunoassay (EIA), immunodiffusion (ID), and complement fixation (CF) tests for antibody to the A antigen of Blastomyces dermatitidis were assessed in 47 patients in an epidemic of blastomycosis and in 89 control subjects with lower respiratory tract illness. Antibody was detected by EIA, ID, and CF in 77%, 28%, and 9% of the patients, respectively. EIA titers ranged from 1:8-1:512 (median titer, 1:128). Antibody detected by ID or CF was always detectable by EIA. Antibody was detected by EIA 13 days after illness onset, and the peak seroprevalence rate and geometric mean titer occurred 50-70 days after onset. Antifungal therapy produced a significant decline in antibody titer by approximately six months after onset. Seven (8%) control subjects had detectable antibody, six had EIA titers of 1:8, and one had a titer of 1:16. The specificities for EIA, ID, and CF were 92%, 100%, and 100%, respectively. The EIA provides a significant advance in serodiagnostic testing for blastomycosis and can be used in an outbreak setting as an epidemiological tool to identify acute B. dermatitidis infection; titers greater than or equal to 1:32 strongly support the diagnosis, whereas titers of 1:8 or 1:16 are suggestive.

Immunological responses and the role of the paralyzing toxin in rabbits infested with Rhipicephalus evertsi evertsi.

Twenty-nine rabbits were exposed to 4 infestations with 20, 50, and 100 adult red-legged ticks (Rhipicephalus evertsi evertsi). Upon challenge, 16 rabbits (55%) contracted paralysis, and 14 of these (88%) died. Most deaths occurred in rabbits challenged with 100 ticks. Immunity to paralysis and subsequent resistance to tick feeding developed in the hosts that survived the initial challenge. Antibody titers to a salivary gland antigen increased progressively as determined by the following tests: passive hemagglutination, agar gel double immunodiffusion, and enzyme-linked immunosorbent assay. Rabbits challenged with 20 ticks displayed declining titers with advanced frequency of challenge and few of the rabbits in this group developed paralysis. There was no decline in antibody titers in groups of rabbits exposed to 50- and 100-tick loads. It is suggested that a certain quantum of antigen injected by the ticks is necessary for induction of immunity to paralysis.

Long-term antibody response after measles vaccination in an isolated arctic society in Greenland.

Scoresbysund is an isolated district on the east coast of Greenland with 500 inhabitants, mainly Polar Eskimos, which had never been exposed to natural measles. In 1968 more than 90% of the population were vaccinated with the Schwarz live further-attenuated measles vaccine and subsequently children born after 1968 likewise received the measles vaccination. Upon the initial measles vaccination no clinical cases of measles have been observed. The immunity status of the isolated population has been followed for 16 years after vaccination by IgM, IgA, and IgG ELISA tests and by HI test on a series of serum samples taken at intervals. Immunoblotting was performed on sera obtained 16 years after the vaccination. In general, antibody studies have demonstrated some decline in antibody titres after the initial measles vaccination. However, a temporary moderate increase in measles antibodies occurred in some individuals 2-4 years after vaccination, probably due to a reinfection of vaccinees. Most of these individuals did not have demonstrable IgA antibodies prior to the supposed reinfection.

A Rift Valley fever vaccine trial: 2. Serological response to booster doses with a comparison of intradermal versus subcutaneous injection

A booster dose of a formalin-inactivated, cell culture-propagated Rift Valley fever vaccine (TSI-GSD-200) was administered without significant reactogenicity to 60 volunteers 18 months after they received a three dose primary series. Blood was drawn for serological testing prior to boosting and 10, 49, and 180 days thereafter. Neutralizing antibody response was prompt, being maximum on day 10 and considerably higher than the peak titres obtained on day 42 after the initial series. A marked decline in antibody titres was evident by day 180, as seen for the primary series, but residual titres were substantially higher. The initial series was given in doses of 1.0, 0.5, 0.3, or 0.1 ml and the immune status achieved with these injections was a major determinant of the response to boostering. Secondary responses were highly dependent in magnitude and duration on the prior immune status of the recipient. Evaluation of dose and route of recall inoculation showed 1.0 ml given subcutaneously (SC) to be equivalent to 0.1 ml administered intradermally (ID), though inference should be guarded due to the small sample size. Although 0.1 ml SC dose was inferior to either, it was modestly effective. Intradermal administration of vaccine may be useful for extending the small reserve of vaccine available for use in emergency.