Losonsky G A, Yunyongying J, Lim V, Reymann M, Lim Y L, Wasserman S S, Levine M M
Department of Medicine, University of Maryland, Baltimore 21201, USA.
Infect Immun. 1996 Jan;64(1):10-5. doi: 10.1128/iai.64.1.10-15.1996.
Although serum vibriocidal activity is used extensively as a marker of immunity to O1 Vibrio cholerae, there are limitations in this assay to detect instances of reexposure. We define the conditions operative in producing secondary vibriocidal responses in North American volunteers primed with either wild-type V. cholerae 1, 4, or 6 months later. Secondary serum vibriocidal responses occurred under two distinct secondary challenge conditions. The first occurred when secondary challenge produced a breakthrough in clinical protection. Following secondary exposure, 14 of 22 (64%) and 1 of 29 (3%) subjects with and without vibrio stool excretion, respectively, had secondary responses (P < 0.001); 5 of 6 (83%) and 10 of 45 (22%) subjects with or without diarrhea, respectively, mounted a secondary response (P = 0.006). The second condition occurred in the presence of full clinical protection but was dependent on the time interval between exposure. No subject (0 to 17) vaccinated with CVD 103-HgR and given homologous wild-type challenge within 4 months mounted a secondary vibriocidal response (P = 0.0009). The majority of the serum vibriocidal activity was of the immunoglobulin M (IgM) isotype, seen in 96 and 73% of subjects following primary and secondary exposure, respectively. Vibriocidal activity in the IgG fraction following primary and secondary exposures occurred with < or = 50% of volunteers; lipopolysaccharide (LPS)-specific IgG1 and IgG3 subclass responses supported the vibriocidal isotype data. However, following primary exposure, IgG4 LPS responses predominated, occurring in 81% of responding volunteers. These data suggest that, under certain conditions of secondary exposure to V. cholerae O1 antigens, when there is sufficient active local immunity present, there is a block of vibrio antigen resampling at the M cell level. We discuss the implications of and possible explanations for these findings.
尽管血清杀弧菌活性被广泛用作对O1群霍乱弧菌免疫力的标志物，但该检测方法在检测再次暴露情况时存在局限性。我们确定了在北美志愿者中，分别在初次接种野生型霍乱弧菌1、4或6个月后产生二次杀弧菌反应的操作条件。二次血清杀弧菌反应在两种不同的二次激发条件下出现。第一种情况发生在二次激发导致临床保护出现突破时。二次暴露后，有和无弧菌粪便排泄的22名受试者中的14名（64%）和29名受试者中的1名（3%）分别出现了二次反应（P<0.001）；有或无腹泻的6名受试者中的5名（83%）和45名受试者中的10名（22%）分别出现了二次反应（P = 0.006）。第二种情况发生在具备完全临床保护的情况下，但取决于暴露之间的时间间隔。在4个月内接种CVD 103-HgR并接受同源野生型激发的受试者中，没有一名（0至17名）出现二次杀弧菌反应（P = 0.0009）。大部分血清杀弧菌活性属于免疫球蛋白M（IgM）同种型，分别在初次和二次暴露后的96%和73%的受试者中可见。初次和二次暴露后，IgG组分中的杀弧菌活性在≤50%的志愿者中出现；脂多糖（LPS）特异性IgG1和IgG3亚类反应支持了杀弧菌同种型数据。然而，初次暴露后，IgG4 LPS反应占主导，在81%的有反应志愿者中出现。这些数据表明，在二次暴露于O1群霍乱弧菌抗原的某些条件下，当存在足够的活跃局部免疫时，在M细胞水平上存在弧菌抗原再取样的阻断。我们讨论了这些发现的意义和可能的解释。
