Lagos R, San Martin O, Wasserman S S, Prado V, Losonsky G A, Bustamante C, Levine M M
Centro para Vacunas en Desarrollo-Chile, Santiago.
Pediatr Infect Dis J. 1999 Jul;18(7):624-30. doi: 10.1097/00006454-199907000-00011.
Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age.
The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated.
Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose.
Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.
口服霍乱活疫苗CVD 103-HgR以5×10⁹菌落形成单位的单剂量给予成人、学龄儿童和学龄前儿童时，耐受性良好且具有免疫原性。由于单剂量接种后引发免疫反应对于任何年龄组的任何口服疫苗来说都很罕见，因此CVD 103-HgR被用作探针，以研究该疫苗在3至17个月大的婴幼儿中的临床可接受性、实用性和免疫原性。
该研究先后纳入了12至17个月大的婴儿（n = 104）、7至11个月大的婴儿（n = 106）和3至5个月大的婴儿（n = 102）。一半的受试者被随机分配接受疫苗，另一半接受安慰剂，采用双盲方式。在双盲随访2周后，所有受试者都接受了一剂疫苗。在基线以及每次接种后2周采集的编码血清中检测杀弧菌抗体滴度。缓冲疫苗“混合剂”的体积为100毫升；摄入≥70毫升的受试者被视为完全接种。
总体上只有37%的受试者（3至5个月大婴儿中的25%）摄入了≥70毫升的混合剂。该疫苗耐受性良好，接种疫苗与安慰剂后不良反应的发生率或严重程度无显著差异。在完全接种的受试者（66%）和摄入较少剂量疫苗混合剂的受试者（63%）中，单剂量摄入CVD 103-HgR后的血清转化情况相似。在摄入两剂的受试者中，118人中有5人在第一剂接种后第7天排出了疫苗菌株，而在第二剂接种后118人中无人排出。
单剂量口服CVD 103-HgR在婴儿中耐受性良好且具有免疫原性，即使摄入部分剂量也是如此。年长儿童容易接受的缓冲疫苗混合剂对小婴儿没有吸引力，必须寻找改进的疫苗配方和给药载体来为婴儿接种疫苗。
