Japanese encephalitis vaccine (inactivated, BIKEN) in U.S. soldiers: immunogenicity and safety of vaccine administered in two dosing regimens.

The safety and immunogenicity of Japanese encephalitis (JE) vaccine (Nakayama strain, monovalent / BIKEN) was studied in 538 U.S. soldiers in 1990. Three doses of vaccine from three consecutively manufactured lots were given on days 0, 7, and either 14 or 30. Serum for antibody determination was drawn at months 0, 2, and 6. Japanese encephalitis plaque reduction neutralization tests were performed by three laboratories on each specimen. Five hundred twenty-eight (98%) participants completed the immunization series. All recipients without antibody before immunization developed neutralizing antibody against JE virus. There were no differences in geometric mean titer among the three test lots at months 2 and 6. Soldiers who received the third dose on day 30 had higher titers at both time points. Antibody to yellow fever had no significant effect on immune response to vaccine. Conclusions drawn from analysis of serologic data from the three labs were nearly identical. Symptoms were generally limited to mild local effects and were reduced in frequency with each subsequent does in the series (21% to 11%; P < 0.0001). Generalized symptoms were rare (e.g., fever = 5%) with no reported cases of anaphylaxis.

Efficacy of a two-component acellular pertussis vaccine in infants.

OBJECTIVE: This case-control study investigated the protective efficacy against pertussis of three doses of a two-component acellular pertussis vaccine (manufactured by Biken in Japan) combined with diphtheria and tetanus toxoids (manufactured by Connaught Laboratories in the US) in infants. METHODS: A case-control study was performed in 63 pediatric practices in Germany. Prospective recruitment of 16,780 infants ages 6 to 17 weeks took place between February, 1993, and July, 1994. According to parental choice infants received either Biken acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTacP) (74.6%) at approximately 2, 4 and 6 months of age, or a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine (10.9%), diphtheria-tetanus toxoids vaccine (12.5%) or no vaccine (2.0%). Prospective surveillance of pertussis cases between February, 1993, and May, 1995, was accomplished by culturing all infants < or =2 years of age presenting with cough > or = 7 days. A pertussis case was defined as any cough of 21 days or longer plus a positive Bordetella pertussis culture or household contact exposure. RESULTS: We identified 241 pertussis cases prospectively by 11,017 B. pertussis cultures and 949 controls matched for age were selected from the same pediatric practices. Medical history and demographic and vaccine status data were collected from each case and for four controls. Data were analyzed through conditional logistic regression taking into account individual matching and adjusting for potential confounding variables. DTacP combined with diphtheria and tetanus toxoids vaccine was 82% protective (95% confidence interval, 68 to 90), diphtheria-tetanus toxoids-whole cell pertussis vaccine was 96% protective (95% confidence interval, 78 to 99). Protection against typical B. pertussis infection characterized by paroxysmal cough lasting > or =21 days was 96% (95% confidence interval, 87 to 99) for DTacP and was 97% (95% confidence interval, 79 to 100) for diphtheria-tetanus toxoids-whole cell pertussis vaccine. Adjustment for potentially confounding variables did not change the results significantly. CONCLUSIONS: Three doses of the two-component acellular pertussis vaccine protected infants against pertussis disease during the period before the recommended booster vaccination. For typical pertussis disease as defined by the WHO efficacy was high and similar to that of a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine.

Humoral and mucosal immunity in infants induced by three sequential inactivated poliovirus vaccine-live attenuated oral poliovirus vaccine immunization schedules. Baltimore Area Polio Vaccine Study Group.

The relative immunity induced by sequential administration of inactivated poliovirus vaccine (IPV) produced in human diploid cells and live attenuated oral poliovirus vaccine (OPV) was evaluated by randomization of 510 infants to receive IPV and OPV sequentially according to one of three experimental schedules, IPV only, or OPV only. The antibody response to two IPV doses was lower than expected. However, for each of the IPV-OPV sequential schedules, the first OPV dose significantly enhanced seroconversion rates and geometric mean microneutralization antibody titers. Three months after the final dose, 96%-99%, 99%-100%, and 81%-100% of infants had antibodies to poliovirus types 1, 2, and 3, respectively, and subjects with two or more prior OPV doses were significantly less likely than those with none or one prior OPV dose to excrete virus in feces after an OPV challenge. Sequential IPV-OPV immunization is now recommended for routine use in the United States. The optimal schedule consists of two IPV doses followed by two OPV doses.

Comparison of diphtheria-tetanus-two component acellular pertussis vaccines in United States and Japanese infants at 2, 4, and 6 months of age.

OBJECTIVE: We compared the diphtheria and tetanus toxoids and bicomponent acellular pertussis vaccine (DTaP) responses in Japanese and United States infants. DESIGN: This was a double-blind, comparative study. SETTING: Private pediatric practices in Japan and the U.S. participated. SUBJECTS: One hundred eighty-nine healthy 2-month old infants were tested. INTERVENTIONS: Infants were immunized at 2, 4, and 6 months of age. The Japanese formulation (DTaP-J) contained 20 micrograms of pertussis toxin (PT) and 20 micrograms of filamentous hemagglutinin (FHA); the U.S. formulation (DTaP-US) contained 23.4 micrograms of each antigen. Parents used a standard form to record average adverse experiences. Serum was obtained before the first immunization, 2 months after the second immunization, and 1 month after the third immunization. MEASUREMENTS: Differences in DTaP-J and DTaP-US were evaluated in Japanese infants immunized subcutaneously (s.c.). Differences due to ethnicity and to route of administration were compared in U.S. infants immunized with DTaP-US s.c. or intramuscularly (i.m.). An indirect enzyme-linked immunosorbent assay was used to determine immunoglobulin G antibody responses to PT, FHA, and tetanus toxoid. Neutralizing antibody to PT was measured by a Chinese hamster ovary call assay. Diphtheria antitoxin was assayed by serum neutralization on VERO cells. RESULTS: Statistical differences (P < .05) in adverse events included less fatigue after immunization with DTaP-US compared with DTaP-J. Erythema of more than 2.5 cm was more frequent, but erythema less than 2.5 cm was less frequent in Japanese infants compared with U.S. infants. Fewer Japanese infants were febrile ( > 38 degrees C), tired, or irritable. Subcutaneous immunization resulted in a greater frequency of erythema and induration. The DTaP-US resulted in an equivalent response to PT and a greater response to FHA. More Japanese infants demonstrated at least a fourfold response over preimmunization antibody values to FHA. In U.S. infants, antibody responses to the contained pertussis antigens were equivalent after i.m. and s.c. administration. Compared with Japanese infants receiving DTaP-J s.c., U.S. infants receiving DTaP-US i.m. had equivalent responses to PT and a greater response to FHA. CONCLUSIONS: United States infants receiving an i.m. injection of a U.S. -produced bicomponent DTaP vaccine produced antibody responses to the contained pertussis antigens at least equal to those of Japanese infants receiving a similar bicomponent DTaP vaccine shown to be effective in older Japanese children.

Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period.

OBJECTIVE: To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic. DESIGN: Randomized clinical trial. SETTING: Suburban New Orleans pediatric population. PARTICIPANTS: Convenience sample of 150 healthy infants. METHODS: Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide. RESULTS: The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01). CONCLUSIONS: Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.

Safety and immunogenicity of acellular diphtheria-tetanus-pertussis and Haemophilus conjugate vaccines given in combination or at separate injection sites.

This prospective, double-blind, randomized trial compared the immunogenicity and reactogenicity of acellular diphtheria-tetanus-pertussis vaccine and Haemophilus influenzae type b conjugate vaccine-diphtheria toxoid conjugate, given at separate injection sites or at a single site, in 79 children 18 months of age who had received three prior immunizing doses of whole-cell diphtheria-tetanus-pertussis vaccine. No significant differences were observed.

Prevention of experimental coronavirus colds with intranasal alpha-2b interferon.

Fifty-five volunteers treated with either intranasal recombinant interferon (rIFN; 2 X 10(6) IU/day) or placebo for 15 days were exposed to coronavirus by direct intranasal inoculation on the eighth day of treatment. Symptom scores were recorded, and cultures of virus were taken daily for all volunteers for seven days after inoculation. Nineteen (73%) of the 26 placebo recipients met symptom-score criteria for a cold, compared with 12 (41%) of the IFN recipients (P = .02). The mean nasal symptom scores in the placebo and IFN groups were 9.2 and 5.4, respectively (P = .03), and the mean total symptom scores in the two groups were 23.2 and 9.4, respectively (P = .003). The mean number of days with a total symptom score greater than 4 was 1.6 in the placebo recipients and 0.5 in the rIFN recipients (P = .02). Prophylactic intranasal rIFN effectively shortened the duration and reduced the severity of coronavirus cold symptoms.

A model for obtaining predictable natural transmission of rhinoviruses in human volunteers.

A model has been developed in which rhinoviral colds can be predictably transmitted by experimentally infected donors to susceptible recipients in a continuously monitored and controlled environment under simulated natural conditions. Rates of transmission correlated closely (r = .926, P less than .01) with donor-hours of exposure. This model can be used to define routes of transmission, to explore methods of controlling dissemination, to study resistance mechanisms, and to test preventive and therapeutic agents.

Short-duration exposure and the transmission of rhinoviral colds.

Transmission of infection with rhinovirus type 55 was attempted under natural circumstances of interaction among 26 experimentally infected donors and 33 antibody-free (titer, less than 1:3) recipients. In a total of three experiments, only two recipients (6%) became infected. In the first experiment no transmissions from five donors to nine recipients occurred after 2-3 hr of loud vocalization and card playing in a small room. In the second experiment a cold was transmitted to one (9%) of 11 recipients living in dormitory rooms for 36 hr in groups consisting chiefly of two donors and two recipients. In the third experiment one (8%) of 13 recipients was infected after kissing an infected donor. In studies with rhinovirus type 16, the 50% human infectious dose was found to be 0.28 TCID50 (50% tissue culture infectious dose) in the nose, 2,260 TCID50 on the tongue, and 11,000 TCID50 on the external nares. Rhinoviral infections are difficult to transmit by short-term natural exposure, perhaps because the agent must be present in overwhelming numbers to reach susceptible mucosal cells.