Antibody and Cell-mediated Immunity to Pertussis 4 Years After Monovalent Acellular Pertussis Vaccine at Birth
ABSTRACT In a previous study we found that monovalent acellular pertussis (aP) vaccine at birth and one month achieves higher IgG antibody (Ab) levels to pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) by 8 weeks, with compared to controls. Here we report antibody and cell mediated immune (CMI) responses to 4 years of age.
IgG Ab to PT, FHA and PRN, diphtheria (D), tetanus (T) was measured in the 3 groups (aP vaccine at birth and one month, aP birth only and no aP) at 2 years, and pre and post DTaP-IPV vaccine at 4 years. CMI responses to pertussis vaccine antigens were measured at 2 years. Adverse events following DTaP-IPV were recorded.
52 of 74 subjects (70%) were available for follow up. Overall, 11 (21%) had detectable PT IgG at 2 years, decreasing to 10% pre 4 year old booster compared with 100% at 8 months of age. Post the 4 year booster, pertussis antigen IgG levels were similar, but there was a trend to lower PT IgG levels in birth aP infants (GMC 28.7 EI.U/ml) compared to controls (GMC 53.6 EI.U/ml). Th2 cytokine responses to pertussis antigen stimulation were higher in aP recipients at 2 years. There was no difference in injection site reactions among groups following the DTaP-IPV booster at 4 years old.
In the longest reported follow-up of infants who received aP vaccine at birth, we found a trend to lower PT IgG antibodies post booster compared with receipt of first dose of aP-containing vaccine at 8 weeks of age. Short and long-term antibody responses with and without prior maternal pertussis vaccination are crucial for further evaluation of this strategy for preventing severe early pertussis.
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ABSTRACT: Longitudinal serum samples were collected from 542 children that had participated in a Swedish pertussis vaccine trial 1992-1995 [Gustafsson L, Hallander HO, Olin P, Reizenstein E, Storsaeter J. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 1996;334(6):349-355] and who did not contract pertussis. The sera were analyzed for post vaccination antibody decay and for booster response of anti-PT (IgG antibodies against pertussis toxin), as measured by ELISA. Generally, an initial rapid decay of antitoxin antibody concentration was followed by a slower decay; the change occurring when the geometric mean level of antitoxin concentration reached 8-9 ELISA Units/mL (EU/mL). The time needed to reach this level was 8-9 months after the third dose in a 2, 4, and 6 months schedule. A "best-fit" combined regression model was used to predict when 50% of the children have less than the minimum level of detection of anti-PT (1EU/mL). This occurred about 65 months after dose 3 at an age of 6 years. The anti-PT response to a booster dose was evident but the post-booster geometric mean values decreased with number of years after the third dose and the response appeared later. The results indicate that a pre-school booster might be considered at 6 years of age or earlier.Vaccine 12/2005; 23(46-47):5359-64. DOI:10.1016/j.vaccine.2005.06.009 · 3.49 Impact Factor
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ABSTRACT: Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis) (DTaP) are being progressively introduced into vaccination programs worldwide, with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP) vaccine. The DTaP vaccine has an improved safety profile in infants, but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses. We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP (n = 30) or DTwP (n = 16) and by correlating these parameters, in particular cytokine responses, with expression of local side effects at the injection site. Large local reactions (> or =50-mm diameter) 24 to 72 h after receiving the DTaP booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically "high Th2 responders" as detected by in vitro responsiveness to polyclonal mitogen. Our findings suggest that priming during infancy with DTaP promotes stable, boostable Th2-polarized immunity against vaccine antigens, which in a significant subset of children is subsequently associated with local reactions at the booster site. The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory.Infection and Immunity 12/2005; 73(12):8130-5. DOI:10.1128/IAI.73.12.8130-8135.2005 · 4.16 Impact Factor
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ABSTRACT: This study assessed the persistence of antibodies following primary vaccination with two commercially available, hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccines (Infanrix hexa and Hexavac). The immunogenicity and reactogenicity of booster vaccination with Infanrix hexa were also evaluated. A total of 329 children primed at 2, 4, and 6 months with Infanrix hexa (n=166) or Hexavac (n=163) received booster vaccination with Infanrix hexa at 12-19 months of age. Antibody concentrations were measured immediately before and 1 month after booster vaccination. Prebooster persistence of antibodies to HBs, PRP and poliovirus types was significantly higher in children primed with Infanrix hexa than with Hexavac, both in terms of seroprotection rate and GMCs/GMTs (p < 0.05). Boosting with Infanrix hexa elicited strong immune responses to all antigens irrespective of the primary vaccine used, with post-booster seroprotection rates comparable between the two primary vaccine groups (ranging from 98.1 to 100%). The incidence of clinically relevant solicited symptoms did not differ significantly between primary vaccine groups, even if the incidence of local symptoms appeared to be more frequent in subjects primed with Infanrix hexa than in those primed with Hexavac. In summary, booster vaccination with Infanrix hexa during the second year of life is immunogenic and well tolerated, offering protection irrespective of the primary combination vaccine used.Human vaccines 11/2006; 2(6):249-54. DOI:10.4161/hv.2.6.3432 · 3.64 Impact Factor