Holubová Jana, Staněk Ondřej, Brázdilová Ludmila, Mašín Jiří, Bumba Ladislav, Gorringe Andrew R, Alexander Frances, Šebo Peter
Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic.
Public Health England, Research and Development Institute, Porton Down, Salisbury SP4 0JG, UK.
Vaccines (Basel). 2020 Nov 19;8(4):695. doi: 10.3390/vaccines8040695.
whole-cell vaccines (wP) caused a spectacular drop of global pertussis incidence, but since the replacement of wP with acellular pertussis vaccines (aP), pertussis has resurged in developed countries within 7 to 12 years of the change from wP to aP. In the mouse infection model, we examined whether addition of further protective antigens into the aP vaccine, such as type 2 and type 3 fimbriae (FIM2/3) with outer membrane lipooligosaccharide (LOS) and/or of the adenylate cyclase toxoid (dACT), which elicits antibodies neutralizing the CyaA toxin, could enhance the capacity of the aP vaccine to prevent colonization of the nasal mucosa by . The addition of the toxoid and of the opsonizing antibody-inducing agglutinogens modestly enhanced the already high capacity of intraperitoneally-administered aP vaccine to elicit sterilizing immunity, protecting mouse lungs from infection. At the same time, irrespective of FIM2/3 with LOS and dACT addition, the aP vaccination ablated the natural capacity of BALB/c mice to clear infection from the nasal cavity. While wP or sham-vaccinated animals cleared the nasal infection with similar kinetics within 7 weeks, administration of the aP vaccine promoted persistent colonization of mouse nasal mucosa by
全细胞疫苗(wP)曾使全球百日咳发病率大幅下降,但自从用无细胞百日咳疫苗(aP)取代wP以来,在从wP转换为aP后的7至12年内,发达国家百日咳疫情又死灰复燃。在小鼠感染模型中,我们研究了在aP疫苗中添加更多保护性抗原,如带有外膜脂寡糖(LOS)的2型和3型菌毛(FIM2/3)和/或能诱导中和CyaA毒素抗体的腺苷酸环化酶类毒素(dACT),是否能增强aP疫苗预防 在鼻黏膜定植的能力。添加类毒素和能诱导调理抗体的凝集原适度增强了腹腔注射aP疫苗已有的诱导无菌免疫的高能力,保护小鼠肺部免受 感染。同时,不管是否添加了带有LOS的FIM2/3和dACT,aP疫苗接种都消除了BALB/c小鼠从鼻腔清除 感染的天然能力。虽然wP疫苗接种或假接种的动物在7周内以相似的动力学清除了鼻腔感染,但aP疫苗接种促进了 在小鼠鼻黏膜的持续定植