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Development of a vaccine for prevention of congenital cytomegalovirus (CMV) disease is a priority. This study evaluated a "prime-boost" strategy by comparing the safety and immunogenicity of 3 doses of subunit CMV glycoprotein B (gB) vaccine plus MF59 (a squalene-in-water emulsion), 2 doses of a canarypox recombinant vaccine expressing CMVgB (ALVAC-CMVgB) followed by 2 doses of the subunit gB vaccine, 3 doses of both vaccines administered concomitantly, and placebo in 105 healthy, CMV-seronegative adults. Systemic adverse events were rare, but local reactions were common in all groups. After the first subunit vaccination, neutralizing antibody titers in the prime-boost group were comparable to those in subjects receiving 2 subunit vaccinations, indicating a priming effect of ALVAC-CMVgB. However, after the final dose, antibody and cell-mediated immune responses were not significantly different among the groups. All 3 vaccine regimens induced high-titer antibody and lymphoproliferative responses, but no benefit for priming or simultaneous vaccination was detected.

To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.

The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8 + . Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.

Serial serum samples from a 2-year human trial of outer surface protein (Osp) A vaccine were analyzed by Borrelia burgdorferi growth-inhibition assay (GIA) and anti-OspA ELISA to assess the antibody responses of vaccine recipients and subjects with Lyme disease. Although 74% of OspA recipients had a reciprocal GIA titer >/=64 after 3 vaccinations, none of the placebo recipients, even those with Lyme disease, had a GIA titer this high. The correlation between GIA and ELISA titers after 3 doses of vaccine was.84; however, more vaccine recipients had an elevated ELISA titer paired with low GIA titer than had a low ELISA titer with a high GIA titer. OspA-vaccine recipients who acquired Lyme disease had significantly lower serum GIA and ELISA titers after 3 immunizations than did age- and sex-matched OspA recipients without Lyme disease. Thus, vaccinated subjects had antibodies to native antigen on viable cells, and antibody assays with this specificity may predict protection of vaccinees against infection.

Clinical and serum antibody responses following intramuscular injection of two formulations of Salmonella typhi Vi capsular polysaccharide (Vi) were assessed in a double-blind evaluation. Healthy adults were randomly assigned to receive a 25 micrograms dose of liquid (Vi-Liq; n = 182) or freeze-dried Vi vaccine (Vi-Lyoph; n = 55), or placebo (n = 86). Erythema and/or indurationor = 1 cm in diameter at the injection site developed in 13/182 (7%) of Vi-Liq and 3/55 (5%) of Vi-Lyoph recipients (not significant, n.s.). Fever (oral temperatureor = 100 degrees F (37.8 degrees C)) occurred in2% of vaccinees. The frequencies of rises of fourfold or greater and of maximal Vi antibody levels were similar in the two vaccine groups. Fourfold or greater rises in serum Vi antibody levels (RIA) developed in 53% of Vi-Lyoph and 60% of Vi-Liq recipients by 1 week (n.s.), and 98 and 93%, respectively, by 1 month (n.s.). The frequencies of adverse reactions and mean Vi antibody levels following booster immunization with Vi-Liq 27 to 34 months after primary immunization (n = 55) were similar to those observed following primary immunization, although subjects given a booster dose were more likely to develop local reactionsor = 1 cm in diameter than those given a first dose (10/55 versus 13/182, p = 0.013 by the chi 2 test). Primary and booster immunizations with the Vi vaccines are well tolerated in healthy adults; mean Vi antibody levels remain significantly elevated for up to 34 months after primary immunization.

We immunized 24 patients (mean age 15.2 +/- 9.3 months) with polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) 2 months after a systemic Haemophilus influenzae type b infection. Children less than 24 months of age were immunized twice. Serum was obtained for antibody to PRP before and 1 or 2 months after immunization. Three of five children greater than 24 months of age and three of six children 18 to 24 months of age developed greater than 1 microgram/ml of antibody after immunization, and geometric mean postimmunization levels were significantly greater than preimmunization levels for both groups. However, two children who failed to respond to conventional PRP vaccine did not respond as expected to one dose of PRP-D. For children 7 to 17 months of age, the geometric mean PRP antibody levels increased as follows: preimmunization, 0.05 micrograms/ml; after the first dose, 0.28 micrograms/ml (p = 0.003); and after the second dose, 3.39 micrograms/ml (p = 0.001). Of 13 children, 10 developed antibody values greater than 1.0 micrograms/ml. PRP conjugate vaccines are immunogenic in young children who have not developed protective PRP antibody levels after a systemic H. Influenzae type b infection.

Forty healthy adult males were given a 20-micrograms intramuscular dose of either a new recombinant hepatitis B virus (HBV) vaccine produced in mammalian cells (rHBsAg) or the currently licensed HBV vaccine derived from human plasma (HEPTAVAX-B), and booster doses were administered one month and six months later. The percentage of vaccinees who seroconverted on the 10th and 30th days after the first vaccination was higher for the rHBsAg vaccinees than for the recipients of plasma-derived vaccine (rHBsAg: 10% on day 10 and 70% on day 30; HEPTAVAX-B: 0% and 25%, respectively). The only statistically significant difference in titers of antibody to HBV surface antigen was noted 30 days after the first vaccination. Both vaccines induced a shift in antibody from the 19S to the 7S fraction and a specific antibody response to the a determinant. The rHBsAg vaccine was not associated with significant reactogenicity or toxicity and was somewhat more immunogenic than the currently licensed product.

The reactogenicity and immunogenicity of whole-virus and split-product influenza vaccines were studied in 77 children between the ages of 6 and 36 months. Subjects initially received monovalent vaccine containing either A/USSR/77 (H1N1) antigen in 1978 or A/Brazil/78 (H1N1) antigen in 1979. One month later a trivalent preparation was given which contained the respective H1N1 antigen plus A/Texas/77 (H3N2) and B/Hong Kong/72 antigens. Temperatures of ≥37.8 C (≥100 F) were observed more commonly after initial vaccination with whole-virus vaccine (35%) than after split-product vaccine (14%). No child had a temperature of ≥39.4 C (103 F) or a febrile convulsion. The trivalent vaccines were more reactogenic than the monovalent vaccines although none of the reaction indices exceeded 0.9. The whole-virus vaccine appeared to be more immunogenic, especially in those children who were initially seronegative (preimmunization hemagglutination-inhibiting antibody titer

Naturally acquired humoral immunity is thought to protect adults against serious infections due to Haemophilus influenzae type b (Hib). Antibody to the polyribosylribitol phosphate (PRP) capsule is generally considered protective; antibody to lipooligosaccharide (LOS) or outer membrane protein (OMP) may also play a role. Serum from 23 of 50 healthy young adults had no bactericidal effect (BE) against Hib yet opsonized these organisms for approximately 30% uptake by polymorphonuclear leukocytes. The degree of bactericidal and opsonizing activity in serum from the other 27 subjects generally correlated with the level of antibody to PRP but not to LOS or OMP. However, serum from some individuals had levels of antibody to PRP as high as 4.9 micrograms/ml without BE, and seven of 27 subjects with BE had antibody levels of less than 1 microgram/ml. After vaccination with 20 micrograms of conjugated PRP, the level of antibody to PRP was greater than 5 micrograms/ml in all 50 subjects. BE appeared in 22 of those who originally lacked it, and opsonization increased to approximately 50%.

Clinical and serologic responses to inactivated influenza virus vaccines were studied in 444 children in Los Angeles under doubld-blind, placebo-controlled protocols. One- and two-dose regimens employing monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) vaccine were studied in separate trials. In a single dose, whole-virus vaccines were more potent than split-product vaccines as primary inducers of immunity against influenza A/New Jersey/76 virus. Split-product vaccines were better tolerated clinically and, after two-dose regiments, produced rates of seroconversion (greater than 90%) against A/New Jersey/76 virus comparable to those produced by two doses of whole-virus vaccines. Analysis of heterotypic antibody responses induced by monovalent A/New Jersey/76 vaccines revealed only slight increases in antibody against influenza A/Victoria/75 virus. After vaccination with bivalent vaccines, levels of antibody against influenza A/Victoria/75 virus were significantly higher in subjects who received high doses of split-product vaccines than in subjects who received whole-virus vaccines.

The release of insulin and its A and B chains from the isolated rat islets of Langerhans has been demonstrated by radioimmunoassay. Continued oxygen consumption and incorporation of C 14 leucine into insulin and its peptides substantiated the viability of the preparation. Both insulin and its A and B peptides appear in the medium after incubation, with the peptides predominating in a molar ratio of about 5:1. Insulin and the peptides are demonstrable in the microsomal and soluble fractions of the islets. Insulin appears in the soluble fraction only in the presence of high glucose concentrations. C 14 leucine is incorporated at a higher order of magnitude into insulin than into its peptides, suggesting that the peptides are not in the direct pathway to the biosynthesis of insulin.

A 16 μg dose of HBsAg prepared by the National Institute of Allergy and Infectious Diseases was administered to 71 children, 18 months to 16 years old. The frequency of seroconversion reached 59% (range: 50–78%) at two weeks following the first dose of vaccine and approached 100% one month after the second dose. There were virtually no side effects. Children less than three years of age developed significantly greater anti-HBs responses than did older children or adults. This appears to be related to the greater dose in μg kg −1 administered to these children. Anti-HBs responses (mIU ml −1 ) to the vaccine by the Oriental participants were lower at each sampling interval. Our data suggest that prolonging the third dose of vaccine past six months (e.g. to 12 months) may not significantly alter the eventual antibody levels attained by the vaccinees, but may result in suboptimal protection between the second and third dose in some of them.

Illness associated adenovirus infection is described in 15 immunocompromised patients. Patients were immunocompromised by severe underlying disease, immunosuppressive or corticosteroid therapy or by age (prematurity). Evidence of adenovirus infection was obtained by either viral isolation or, in two cases, characteristic adenovirus inclusion bodies at postmortem study. All clinical illness was associated with high fever (temperature greater than 39 degrees C). Eighty per cent of the patients had severe systemic complaints including malaise, lethargy, fatigue and night sweats; a similar number of gastrointestinal symptoms. Pulmonary complaints were described in 11 of 15 cases and included cough (67 per cent) and tachypnea (53 per cent). Roentgenologic evidence of pneumonia was demonstrated in 12 of 15 patients (80 per cent). Elevation of serum hepatic enzyme levels (serum glutamic pyruvic transaminase (SGPT)) occurred in eight of 11 patients (73 per cent) and was moderate to severe (serum glutamic pyruvic transaminase greater than 450 IU/liter) in five of 11 (45 per cent). Nine patients died; seven after a rapid downhill course and two after a prolonged illness. Evidence of adenovirus infection microscopically by autopsy in the lung, liver or both is demonstrated in four patients with fulminant systemic illness. Adenovirus infection should be considered in the etiology of severe overwhelming illness in the immunocompromised host.

A group B Neisseria meningitidis serotype protein vaccine was studied clinically in adults. The vaccine comprised lipopolysaccharide-depleted outer membrane vesicles from a serotype 2b strain, 3006-M2, noncovalently complexed with group B meningococcal polysaccharide. Volunteers received 25 micrograms each of protein and polysaccharide administered intramuscularly either in 0.9% NaCl or adsorbed onto aluminum hydroxide on weeks 0 and 6. Most individuals experienced mild local reactions, but there were no systemic reactions. Both vaccine formulations stimulated antibodies to the outer membrane proteins of serotypes 2a:P1.2 and 2b:P1.2, but higher levels were achieved with the aluminum hydroxide-adsorbed vaccine after two immunizations. Vaccine-induced antibodies were primarily IgG and were bactericidal for both a serotype 2a and a serotype 2b strain. Induction of bactericidal antibodies has been shown to be a major predictor of protection against meningococcal disease.

During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.

The role of adenovirus as an etiologic agent of hepatic damage has been controversial. A fatal case of adenovirus infection with fulminant hepatitis in a young immunosuppressed adult patient is presented. Intranuclear inclusions were confined to the liver. Electron microscopy revealed crystalline arrays of virions within hepatocytes. This is apparently the first reported case of adenovirus hepatitis occurring in an adult. Adenovirus hepatitis represents another hazard for the immunosuppressed patient.

To evaluate the safety and immunogenicity of the Haemophilus influenzae type b polysaccharide vaccine, PRP, and a new polysaccharide-diphtheria toxoid conjugate vaccine, PRP-D, a collaborative study was carried out in six centers in five states. Subjects were 585 infants 15 to 24 months of age. They were randomly assigned to receive a single dose of PRP or PRP-D vaccine. There were no significant differences in the rate of adverse reactions between the two vaccine groups. Minor local reactions occurred in 10.3% of PRP and 12.5% of PRP-D recipients, and fever in 27.4% of PRP and 23.8% of PRP-D recipients. All reactions resolved within 48 hours. Serum samples were obtained just before vaccination and after 1 month. Prevaccination antibody levels were similar for the PRP (0.035 micrograms/mL) and PRP-D (0.027 micrograms/mL) groups, with no differences in levels by age, sex, race, vaccine lot, or study site. Both groups had significant rises in geometric mean levels, but this difference was significantly greater for PRP-D (2.166 micrograms/mL) than for PRP (0.154 micrograms/mL). In addition, the percentage of responders as determined by three definitions (twofold titer rise, greater than 0.15 micrograms/mL, and greater than 1.0 micrograms/mL) was also significantly greater for PRP-D than PRP. In contrast to a marked age-related immunogenicity to PRP (P less than 0.001), there was no significant variation in immune response to PRP-D by age. PRP-D conjugate vaccine appears to be as safe and significantly more immunogenic than PRP vaccine for children vaccinated at 15 to 24 months of age.

Serum neutralizing antibody and influenza B-specific lymphocyte blast transformation responses were measured in 110 adults and children after an influenza B outbreak. Serum neutralizing antibody and lymphocyte blast transformation responses were seen in 67 to 75% of adults and children recently infected (less than 1 year), but significant lymphocyte blast transformation responses were seen in only 25% of those whose infection was remote (greater than or equal to 3 years). The frequencies of influenza B-induced lymphocyte blast transformation and serum neutralizing antibody responses were similar in the adults and children with similar infection histories.

One hundred adult volunteers were administered inactivated vaccine (20 micrograms/0.5 cc) intramuscularly (IM) or intranasally (IN), or 10(4.7) TCID50 of a live cold-adapted vaccine (CR35) IN. Microneutralization (Nt) and radioimmunoprecipitation methods were employed to measure hemagglutinin antibody responses in sera, nasal washes, and in bronchopulmonary lavage fluids. In unprimed recipients, the relative frequency of serum antibody response and magnitude of rise was highest following the IM-inactivated vaccine (100%) and lowest after IN-live vaccine (29%). However, in individuals with pre-existing antibody, the three vaccines given were comparably immunogenic. Occurrences of secretory IgA hemagglutinin antibody in nasal washings were more frequently associated with topical administration of live or inactivated vaccine, whereas, IgG hemagglutinin antibody responses occurred with equal frequency in nasal washings in all three vaccine groups. Analysis of the hemagglutinin antibody responses in the lower respiratory tract showed that the IN-live vaccine favored the induction of secretory IgA hemagglutinin antibody and the IM-inactivated vaccine stimulated a more frequent IgG hemagglutinin antibody response.

Bactericidal and enzyme-linked immunosorbent assays were used to determine the immunoglobulin classes responsible for group- and type-specific immunity to Neisseria meningitidis among healthy, unvaccinated individuals and persons who received group-B N meningitidis polysaccharide-serotype-2 protein vaccine. Bactericidal antibodies to the group B polysaccharide were primarily IgM; only a few individuals had both IgM and IgG antibodies. IgG bactericidal antibodies were detected only in those individuals with high IgM-antibody levels to group B meningococci. Increased levels of bactericidal antibodies to the group-B polysaccharide were infrequently found in vaccinees, possibly because of high prevaccination bactericidal-antibody levels. Bactericidal antibodies to the group-C polysaccharide were IgM, IgG, or both. Vaccine-induced antibodies to lipopolysaccharide were not bactericidal for a group-C serotype-2 strain with the lipopolysaccharide immunotype of the vaccine strain.

Safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) was evaluated in infants seven to 14 months of age. PRP-D (80% of subjects) or saline placebo (20%) was randomly and blindly administered (two doses separated by two months). Incidence of mild reactions lasting less than 48 hr did not differ significantly between the placebo and vaccine recipients. Preimmunization levels of antibody to PRP were less than or equal to 0.15 micrograms/ml in 97% of subjects. A twofold increase in antibody concentration occurred in 88% of subjects following the first dose and in 99% following the second dose of vaccine. No change occurred in placebo recipients. Mean level of antibody and percentage of subjects with levels of antibody greater than or equal to 1 microgram/ml after vaccination increased with increasing age. Responses were related to vaccine lot but not to sex, race, or geographic location. Two doses of PRP-D in infants seven months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age given the polysaccharide alone.

This case description is from what surely was an influenza epidemic in the year 1557 and is similar to influenzal illnesses seen currently. The pattern of occurrence of influenza is for millions of such cases to occur in epidemics. Hippocrates referred to an epidemic in the year 412 B.C., and history has recorded many influenza epidemics and pandemics since that time. In 1974, an Influenza Research Center (IRC) was established at Baylor College of Medicine (Houston). It has been devoted primarily to obtaining answers to many of the epidemiological questions relat

The character of the immune response to inactivated monovalent influenza A/New Jersey/76 and bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines was studied in children six months to 18 years of age. Titers of hemagglutination-inhibiting antibody in sera taken after vaccination were measured before and after treatment with 2-mercaptoethanol. IgG antibody predominated in responses to the influenza A/Victoria/75 component of bivalent vaccines. In contrast, specific IgM antibody to influenza A/New Jersey/76 virus developed after administration of both monovalent and bivalent vaccines and appeared to characterize the immune response to this antigenic "shift" strain in children. Prevalences of IgM antibody against influenza A/New Jersey/76 virus did not differ significantly by age. This finding implies that type rather than extent of previous experience with influenza determines the IgM antibody response to an antigenic "shifts." Split-product vaccines produced significantly fewer IgM antibody responses to influenza A/New Jersey/76 virus than did whole-virus vaccines, a phenomenon that may correlate with their diminished reactogenicity and immunogenicity in children.

Cellular and humoral immunologic responses were measured in 39 families, 109 members (72 children) following the 1980 influenza B epidemic. Virologic and/or serologic evidence of recent infection was detected in 19 families (36 children and 17 adults) with information on infection in 1977 available for most. Ficollhypaque separated peripheral blood lymphocytes were obtained on all 109 family members 2-12 weeks post-infection and lymphocyte transformation (LT) studies performed with influenza B antigen. LT responses were seen in 28/36 children and 11/17 adults with recent infection; 9/21 children and 6/22 adults with evidence of remote infection. Thirty-six children (1-5 y.o) have been followed since birth; for 22, this marked their primary infection with influenza B. Significant LT response was seen in 16/22 (3 non-transformers also lacked an antibody response). In 3/16, LT responses were present 4-8 weeks post-infection in the absence of neutralizing antibody (NT). LT was not seen in 15/16 uninfected children. There was a tendency for a linear correlation between LT response and post-influenza NT antibody titer in adults, but no such correlation in children to either pre- or post-infection NT antibody titer. This study demonstrates that primary influenza B infection in young children elicits cellular immune responses equivalent to that of adults. LT responses is higher in recent (73%) as compared to remote (35%) infections and there was no correlation with the NT antibody titer achieved.

• Clinical reactions and hemagglutinating-inhibiting (HAI) antibody responses to recent whole-virus and split-product influenza vaccines were studied in 168 children and young adults. The subjects initially received a monovalent vaccine, followed one month later by a trivalent preparation. The reactogenicity of whole-virus and split-product vaccines with an equivalent hemagglutinin content was similar except in the youngest age (6 to 36 months) group in which the whole-virus preparation was more reactogenic. The whole-virus vaccines were more immunogenic, especially in subjects who were previously unprimed (preimmunization HAI antibody titer, ( Am J Dis Child 1982;136:513-517)

WITH the present-day upswing in international travel to six continents, physicians in the United States are likely to be faced with differential diagnostic considerations that include both truly exotic diseases and diseases that are rare because of our immunization practices. In this report, two young adults are described who contracted atypical measles during a European vacation. Report of Cases Case 1.— On July 25, 1977, a 22-year-old woman noted the onset of a pruritic, erythematous, and papular rash on her wrists and abdomen during a flight that was bringing her and her family home from a three-week visit to Central Europe and England. Three days later, generalized aches, fever (temperature, 38.9 to 39.4 °C), chills, and headaches developed. These symptoms persisted for three days. Six days after her return home, she sought medical attention because of severe bilateral flank pain. Chest roentgenogram at this time was interpreted as normal. On

The efficacy of PRP-D vaccine in young infants has been documented in previous studies. We now report the response of patients with IgG subclass deficiency (GSD) to a single immunization with PRP-D. Patients with GSD ranging in age from 6 to 10 years were given a single i.m. dose of 20 μg PRP-D. Total serum anti-PRP antibody levels were determined using a modified Farr assay and radiolabeled PRP. Four patients with GSD and no major abnormalities in B- and T-cell subsets or in vitro mitogen stimulation had a mean preimmunization anti-PRP level of 1.61 μg/ml which rose to 22.6 μg/ml 3-4 weeks after immunization. The mean increase in anti-PRP for 3 patients with IgG2 deficiency was 18.8 μg/ml. Two patients with IgA and IgG2 deficiency responded with post-immunization anti-PRP levels of 10.8 and 40 μg/ml. Both of these patients failed to respond to immunization with a polyvalent pneumococcal polysaccharide (PS) vaccine. One patient with isolated IgG3 deficiency responded normally to diphtheria and tetanus toxoid, to 3 of 4 pneumococcal serotypes tested, and had a rise of anti-PRP antibody from 0.6 to 28.4 μg/ml. A fifth patient with common variable immunodeficiency had no response to immunization with any of the above vaccines. These data suggest that protein conjugate vaccines may lead to effective immunization of patients with defective PS antigen processing.

During a measles immunization campaign blood samples were collected from 203 children before vaccination. Follow up specimens were collected from 125 children 3 wks. later and from 88 children 10 mos. later. Of the 125 children with follow up study, 88 had been previously vaccinatedt 10 had a history of measles and 27 denied vaccination or illness. Measles HAT antibody geometric mean liters (GMTs) were 13, (day 0), 38 (3 wks.), and 23 (10 mos.). Twenty-six of the 125 had HAI liters of – 5 prior to vaccination and showed a ≥4-fold antibody titer rise. IgM measles antibody was detected in 12 of these children after protein-A and 2-ME treatment with a GMT at 3 weeks and 10 months of 61 and 40 respectively. There was no history of measles exposure or vaccination in this group. In the remaining 14 children with initial titers < 5 no IgM antibody response was detected, and despite a 4-fold increase in HAI titer at 3 wks. (GMT 28), the 10 month titer had dropped considerably (GMT 9). Ten of these 14 children had a history of previous measles vaccination. The remaining 99 children had detectable initial titers between 5 and 320. After grouping these according to their pre-booster titers, no significant change in GMTs was observed when day 0, 3 wk. and 10 mo. results were compared. Our study suggests that HAI antibody titers in children previously immunologically stimulated against measles are not altered significantly by revaccination, even when the pre-booster titers are low or not detectable.

In a multicenter study, 502 normal infants ages 7-14 months were randomized to receive either 2 doses of PRP-D intramuscularly containing 20 ug PRP (80%) or placebo (20%) 6-10 weeks apart. Serum samples were obtained from 25% prior to each injection and 1 month post second dose and tested by Farr-type radioimmunoassay for anti-PRP antibody. Reaction data are available from 400 subjects. The incidence of local erythema at the injection site was 2.4% and irritability 3% in both groups. Two PRP-D recipients had temperatures greater than 1022(R). Among 120 children tested for antibody, 99% of PRP-D recipients demonstrated a two fold or greater rise in anti-PRP compared with 5% of placebo recipients. Median anti-PRP levels in the two groups were 7.0 and 0.012 ug/ml respectively. After 2 doses of PRP-D, 95% had ≥ 0.15 ug/ml antibody protein/ml and 90% had > 1 ug/ml. This study confirms prior observations in 9-14 month olds that PRP-D can induce primary and booster antibody responses in infants over 7 months compatible with protection against H. influenzae b disease.

PRP vaccine is a poor immunogen when administered to some children following Hib infection or their sibs. To date, we have immunized 18 patients (mean age 19 mos., range 7-45 mos; 14 meningitis) with PRP-diphtheria toxoid conjugate vaccine (PRP-D) containing 20 μg PRP. Children were inoculated 1-8 mos. (15 ≤ 2 mos.) post illness with 1 or 2 doses of PRP-D. Serum was obtained for anti-PRP Ab (radioantigen binding assay at Connaught Laboratories) prior to and 1 month post vaccine. Serology is available on 13 patients, 6 of whom were Ab negative ( < 0.012 μg/ml) pre-vac (4 were ≤ 16 mos. when immunized). Anti-PRP rises developed in 11/13 patients and 5/6 pre-vac Ab negative patients. The pre- and post-geometric mean titers were 0.13 and 2.0 μg/ml, respectively (p < 0.001 for log transformed data). One patient (pre-vac Ab neg), a non-responder to routine PRP given at 24 mos., developed 0.28 ug/ml anti-PRP Ab following PRP-D at 26 mos. Anti-PRP Ab developed in 3/3 sibs, (8, 11, and 24 mos.), 2 of whom were Ab negative pre-vac. Our data indicate that young children who may not have developed anti-PRP within 1 or 2 mos. of Hib infection usually respond to 1 or more doses of PRP-D and suggest that children at increased risk for Hib disease will likely respond to PRP conjugate vaccines.

Twenty-seven subjects in 1978-79 received monovalent (M) A/USSR/77 (H1N1) (3.5 ug HA) vaccine followed 1 month later by trivalent (T) A/USSR/77, A/Tex/77 and B/HK/72 (10.5 ug HA) vaccine. In 1979-80 50 subjects received similar immunization but the H1N1 component was A/Brazil/78. Forty-one subjects received WV and 36 SV vaccine. Reactions (expressed as reaction index) following M vaccine were WV 0.54, SV 0.38 and after T vaccines were WV 0.90, SV 0.33. No child had temperature >103°F. The percentages of HAI antibody titers ≥1:20 by antigen were as follows: H1N1 - 1 dose WV 35%, SV 30%; H1N1 2 doses WV 97%, SV 72%; A/Tex - WV 92%, SV 97%; B/HK - WV 62%, SV 53%. An IgM antibody response (as demonstrated by a ≥4-fold reduction in titer with 2-ME treatment) was noted more frequently following WV vaccine (38%) than following SV vaccine (13%). As employed in this study the monovalent WV vaccine was of equal reactogenicity to the SV vaccine and though the WV trivalent vaccine had a higher reaction index, it was still within acceptable limits. Since the immunologic response following WV vaccine more closely resembled a natural response (IgM antibody) and was more inmunogenic against the recently isolated H1N1 viruses, it may be a better vaccine for the initial immunization of unprimed children. As in previous studies with A/NJ/76 vaccine, two doses of either vaccine were necessary to produce an adequate response to the H1N1 virus.

AUGMENTED ANTIBODY (Ab) RESPONSES IN INFANTS ADMINISTERED A NEW HAEMOPHILUS INFLUENZAE TYPE B CAPSULAR POLYSACCHARIDE (PRP) DIPHTHERIA TOXOID CONJUGATE VACCINE (PRP-D)

828 INTRANASAL ADMINISTRATION OF LIVE ATTENUATED MEASLES VACCINE IN SIX MONTH OLD INFANTS. A PRELIMINARYTRIAL

MUCOSAL AND SERUM ANTIBODY (Ab) RESPONSES TO PARENTERAL IMMUNIZATION OF 1-YR-OLD INFANTS WITH H. INFLUENZAE B CAPSULAR (PRP) ANTIGEN CONJUGATED TO A DIPH IHERIA PROTEIN CARRIER