口服霍乱疫苗 CVD103-HgR 接种后的抗-O 特异性多糖（OSP）免疫应答与感染野生型霍乱弧菌 O1 埃尔托 因 巴氏后对霍乱的保护作用相关，这在北美的志愿者中得到了证实。
Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers.
机构信息
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
出版信息
PLoS Negl Trop Dis. 2018 Apr 6;12(4):e0006376. doi: 10.1371/journal.pntd.0006376. eCollection 2018 Apr.
BACKGROUND
Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae are involved in mediating protection against cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral cholera vaccine CVD 103-HgR, and whether such responses correlate with protection against cholera.
METHODOLOGY
We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral cholera vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination.
PRINCIPAL FINDINGS
Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = -0.44, P = 0.002; r = -0.36, P = 0.01; respectively), and none of 27 vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01).
CONCLUSION
Oral vaccination with live attenuated cholera vaccine CVD 103-HgR induces antibodies that target V. cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. cholerae O1.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01895855.
背景
霍乱是一种由产毒霍乱弧菌 O1 型和偶尔的 O139 型引起的急性大量脱水性腹泻病。越来越多的证据表明，针对霍乱弧菌 O 特异性多糖（OSP）的免疫反应参与介导对霍乱的保护。因此，我们评估了口服减毒霍乱疫苗 CVD 103-HgR 接种后是否会产生针对 OSP 的抗体反应，以及这种反应是否与预防霍乱有关。
方法
我们评估了 46 名接受 5×108 个菌落形成单位（CFU）口服霍乱疫苗 CVD 103-HgR 接种的北美成年志愿者，然后在接种后 10 或 90 天，通过口服接受约 1×105 CFU 的野生型霍乱弧菌 O1 El Tor Inaba 菌株 N16961 的挑战。
主要发现
接种疫苗后 10 天内，可诱导显著的血清 IgM 和 IgA 抗 OSP 和杀弧菌抗体反应。抗 OSP 和杀弧菌抗体反应之间存在显著相关性。接种后第 10 天的 IgM 和 IgA 抗 OSP 反应与挑战后粪便量减少相关（r = -0.44，P = 0.002；r = -0.36，P = 0.01），27 名接种者中没有 1 人在接种后第 10 天与基线相比任何针对 OSP 的抗体同种型增加≥1.5 倍，在实验性挑战后发生中度或重度霍乱，而在未发生这种抗 OSP 反应的 19 名接种者中，有 5 名发生了（P = 0.01）。
结论
口服减毒霍乱疫苗 CVD 103-HgR 接种可诱导针对霍乱弧菌 OSP 的抗体，这些抗 OSP 反应与实验性霍乱弧菌 O1 挑战后腹泻的保护相关。
试验注册
ClinicalTrials.gov NCT01895855。
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