Cherry James D, Heininger Ulrich, Richards David M, Storsaeter Jann, Gustafsson Lennart, Ljungman Margaretha, Hallander Hans O
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752, USA.
Clin Vaccine Immunol. 2010 May;17(5):741-7. doi: 10.1128/CVI.00469-09. Epub 2010 Mar 24.
In a previous study, it was found that the antibody response to a nonvaccine pertussis antigen in children who were vaccine failures was reduced compared with the response in nonvaccinated children who had pertussis. In two acellular pertussis vaccine efficacy trials in Sweden, we studied the convalescent-phase enzyme-linked immunosorbent assay (ELISA) geometric mean values (GMVs) in response to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM 2/3) in vaccine failures and controls with pertussis. In Germany, the antibody responses to Bordetella pertussis antigens PT, FHA, PRN, and FIM-2 were analyzed by ELISA according to time of serum collection after onset of illness in children with pertussis who were vaccine failures or who were previously unvaccinated. Antibody values were also compared by severity of clinical illness. In Sweden, infants who had received a PT toxoid vaccine and who were vaccine failures had a blunted response to the nonvaccine antigen FHA compared with the response in children who had received a PT/FHA vaccine. Similarly, infants who had pertussis and who had received a PT/FHA vaccine had a blunted response to the nonvaccine antigens PRN and FIM 2/3 compared with the response in children who were vaccine failures and who had received a PT, FHA, PRN, and FIM 2/3 vaccine. In Germany, in sera collected from 0 to 15 days after pertussis illness onset, the GMVs for all 4 antigens (PT, FHA, PRN, and FIM-2) were significantly lower in an unvaccinated group than in children who were diphtheria-tetanus-acellular pertussis (DTaP) vaccine failures. In the unvaccinated group, the GMV of the PT antibody rose rapidly over time so that it was similar to that of the DTaP vaccine recipients at the 16- to 30-day period. In contrast, the antibody responses to FHA, PRN, and FIM-2 at all time periods were lower in the diphtheria-tetanus vaccine (DT) recipients than in the DTaP vaccine failures. In both Sweden and Germany, children with less severe illness had lower antibody responses than children with typical pertussis. Our findings indicate that upon exposure and infection, previous vaccinees have more-robust antibody responses to the antigens contained in the vaccine they had received than to Bordetella antigens that were not in the vaccine they had received. In addition, over time the antibody responses to FHA, PRN, and FIM-2 were greater in children with vaccine failure (primed subjects) than in unvaccinated children (unprimed subjects) whereas the responses to PT were similar in the primed and unprimed children, as determined from sera collected after 15 days of illness. Our findings lend support to the idea that DTaP vaccines should contain multiple antigens.
在之前的一项研究中发现,疫苗接种失败的儿童对非疫苗百日咳抗原的抗体反应,与患百日咳的未接种疫苗儿童相比有所降低。在瑞典进行的两项无细胞百日咳疫苗效力试验中,我们研究了疫苗接种失败儿童和患百日咳的对照儿童在恢复期酶联免疫吸附测定(ELISA)中针对百日咳毒素(PT)、丝状血凝素(FHA)、百日咳杆菌黏附素(PRN)和菌毛(FIM 2/3)的几何平均值(GMVs)。在德国,根据百日咳发病后血清采集时间,通过ELISA分析了疫苗接种失败或之前未接种疫苗的患百日咳儿童对百日咳博德特氏菌抗原PT、FHA、PRN和FIM - 2的抗体反应。还根据临床疾病严重程度比较了抗体值。在瑞典,接种了PT类毒素疫苗且疫苗接种失败的婴儿,与接种了PT/FHA疫苗的儿童相比,对非疫苗抗原FHA的反应减弱。同样,患百日咳且接种了PT/FHA疫苗的婴儿,与疫苗接种失败且接种了PT、FHA、PRN和FIM 2/3疫苗的儿童相比,对非疫苗抗原PRN和FIM 2/3的反应减弱。在德国,在百日咳发病后0至15天采集的血清中,未接种疫苗组所有4种抗原(PT、FHA、PRN和FIM - 2)的GMVs显著低于白喉 - 破伤风 - 无细胞百日咳(DTaP)疫苗接种失败的儿童。在未接种疫苗组中,PT抗体的GMV随时间迅速上升,以至于在16至30天期间与DTaP疫苗接种者的相似。相比之下,白喉 - 破伤风疫苗(DT)接种者在所有时间段对FHA、PRN和FIM - 2的抗体反应均低于DTaP疫苗接种失败的儿童。在瑞典和德国,病情较轻的儿童抗体反应均低于典型百日咳儿童。我们的研究结果表明,在接触和感染后,之前接种过疫苗的儿童对其所接种疫苗中所含抗原的抗体反应,比对其所接种疫苗中未包含的博德特氏菌抗原的反应更强。此外,随着时间推移,疫苗接种失败的儿童(已致敏个体)对FHA、PRN和FIM - 2的抗体反应大于未接种疫苗的儿童(未致敏个体),而根据发病15天后采集的血清测定,已致敏和未致敏儿童对PT的反应相似。我们的研究结果支持DTaP疫苗应包含多种抗原这一观点。