Cellular immunity in adolescents and adults following acellular pertussis vaccine administration.

Cell-mediated immune (CMI) responses to an acellular pertussis vaccine administered to 49 subjects, a subset of participants in the National Institutes of Health-funded adult acellular pertussis vaccine efficacy trial, were evaluated and compared with antibody responses to vaccine antigens. Levels of proliferation of and cytokine secretion from lymphocytes cultured in the presence of pertussis toxin, filamentous hemagglutinin, or pertactin were measured before vaccination and 1 month and 1 year after vaccination. Statistically significant increases in lymphocyte stimulation indices and cytokine secretion were noted at both 1 month and 1 year after vaccination. Brisk pertussis antigen-specific immunoglobulin G responses were also noted at 1 month after vaccination, but these responses had declined by nearly 50% at 1 year after vaccination. These studies clearly demonstrate that both cellular and humoral immune responses occur after the administration of acellular pertussis vaccines to adolescents and adults but that the CMI responses are of greater magnitude and longer duration. CMI responses may be a better correlate of long-term protection.

Bordetella Pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT).

BACKGROUND: Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. METHODS: This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. RESULTS: Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were approximately 5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). CONCLUSIONS: Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants.

Efficacy of an acellular pertussis vaccine among adolescents and adults.

BACKGROUND: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. METHODS: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. RESULTS: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years. CONCLUSIONS: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.

Prevalence of antibody to Bordetella pertussis antigens in serum specimens obtained from 1793 adolescents and adults.

Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.

Acellular pertussis vaccines and complement killing of Bordetella pertussis.

Antibody-dependent complement killing of Bordetella pertussis after immunization with a three-component acellular pertussis vaccine was characterized. Postimmunization activity was unchanged for about half of the adult vaccine recipients. The responses of the other individuals were complex, with evidence of both beneficial and antagonistic responses occurring, sometimes in the same individual.

Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study.

As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.

Antibody-mediated neutralization of pertussis toxin-induced mitogenicity of human peripheral blood mononuclear cells.

Antibody-mediated neutralization of pertussis toxin-induced proliferation of human peripheral blood mononuclear cells (PBMC) was assessed using alamarBlue and compared with results from the Chinese hamster ovary (CHO) cell assay using sera from vaccinated adults and convalescent children. Neutralization values for the CHO assay were similar for vaccinated and convalescent subjects; however. the convalescent group had higher titers in the PBMC assay. Results for pertussis toxin neutralization with the CHO assay appear to be distinct from those with the PBMC assay.

Heptavalent pneumococcal vaccine conjugated to outer membrane protein of Neisseria meningitidis serogroup b and nasopharyngeal carriage of Streptococcus pneumoniae in infants.

BACKGROUND: Streptococcus pneumoniae (Sp) is an important bacterial pathogen in children. Nasopharyngeal (NP) colonization of S. pneumoniae is necessary for person-to-person transmission and often precedes invasive disease. METHODS: NP carriage of Sp was studied in 49 infants following administration of a heptavalent pneumococcal conjugate vaccine (PCV) conjugated to the outer membrane protein of serogroup b Neisseria meningitidis (vaccine serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F). The vaccine was administered at 2, 4, 6, and 12 months of age and carriage rates were compared to a concurrent group of 32 infants not given PCV and evaluated over the first 15 months of life. RESULTS: Overall, Sp was isolated in 86/367 (23%) of NP cultures and 49% of infants. Serotype 23F was significantly less prevalent in the PCV group (1.9%) than the control group (16.1%) (P<0.05). Analysis of the proportion of children with prevalent carriage or acquisition of carriage did not differ between groups when evaluated by age or serotype. We noted, however, decreased acquisition and carriage in the vaccine group 1 month following the 12 month dose of PCV for vaccine serotypes (76 and 52% reduction, respectively), but this did not reach statistical significance (P=0.3). Adjustment for age, daycare and antibiotic use by multivariate modeling revealed no difference in carriage of vaccine containing serotypes or non-vaccine serotypes between groups. CONCLUSION: We did not show a significant effect of this heptavalent PCV on NP carriage. Further study of this issue, including a larger population size, is needed.

Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants.

OBJECTIVE: To evaluate the safety and immunogenicity of two lots of a heptavalent Streptococcus pneumoniae conjugate vaccine (PCV) containing seven capsular polysaccharide serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to the outer membrane complex of Neisseria meningitidis serogroup B (OMPC) and administered to infants at 2, 4, 6, and 12 months of age. METHODS: One hundred twenty infants were randomly assigned to concurrently receive PCV-OMPC and one of two Haemophilus influenzae type b (Hib) conjugate-DTwP combination vaccines: (1) Hib with a heterologous protein carrier (CRM(197), TETRAMUNE, Group 1) or (2) an experimental Hib-hepatitis b combination vaccine with the homologous carrier (OMPC, Group 2). All infants in Groups 1 and 2 received PCV-OMPC (lot 1) at 12 months of age. Another separate group of 120 infants (Group 3) received a different lot of PCV-OMPC concurrently with Hib-CRM(197) (TETRAMUNE) at 2, 4, and 6 months of age and then were randomized to receive either PCV-OMPC or a 23-valent polysaccharide (PS) pneumococcal vaccine at 12 months of age. RESULTS: Each PCV-OMPC lot was generally well tolerated and no vaccine-related serious adverse events were reported. Following the primary series, serotype-specific anti-pneumococcal geometric mean concentrations (GMC) were highest for serotypes 14, 19F, and 4 and lowest for serotypes 6B and 23F. GMC and seroconversion rates in Group 3 (lot 2) were lower than in Group 1 (lot 1) for serotypes 6B, 14, 18C, and 23F. Antibody responses to serotypes 6B, 14, and 18C were significantly lower in Group 2 compared to Group 1. Following a booster dose of PCV-OMPC at 12 months of age, each lot was immunogenic with at least a 5-10-fold increase in antibody levels, and responses were significantly higher among those who received the PS vaccine. CONCLUSIONS: PCV-OMPC is generally safe in infants, displays variable immune response by serotype, and concomitant receipt of Hib vaccine with homologous carrier may impact on its immunogenicity.

Kinetics of maternal hepatitis a antibody decay in infants: implications for vaccine use.

We conducted a seroepidemiologic study to evaluate the kinetics of maternal hepatitis A antibody decay in infants. Serum samples obtained from 200 infants at 2 and 4 months of age were tested for hepatitis A antibody. Seventy-six infants (38%) were hepatitis A antibody-positive with a geometric mean antibody titer of 2634 mIU/ml. Samples collected at 4, 6 and/or 12 months of age showed seropositivity rates of 100, 95 and 39%, respectively. These data indicate that maternal antibody levels remained high through the first 6 months of life but decayed significantly by 12 months of age.