Flores J, Perez-Schael I, Blanco M, Rojas A M, Alfonzo E, Crespo I, Cunto W, Pittman A L, Kapikian A Z
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Clin Microbiol. 1993 Sep;31(9):2439-45. doi: 10.1128/jcm.31.9.2439-2445.1993.
We evaluated the reactogenicity and antigenicity of a quadrivalent rotavirus vaccine composed of serotype 3 rhesus rotavirus (RRV) and three single-gene-substitution reassortants of RRV and human strain D (D x RRV, serotype 1), DS1 (DS1 x RRV, serotype 2), or ST3 (ST3 x RRV, serotype 4) in a double-masked study with 302 infants in Caracas, Venezuela. Three doses of the quadrivalent vaccine composed of either 10(5) PFU (low titer) or 10(6) PFU (high titer) of each component were administered to 99 and 101 infants, respectively, at 4-week intervals starting at the second month of age; 102 infants received a placebo. Postvaccination reactions were monitored by home visits every other day during the week postvaccination. The vaccine was associated with the occurrence of mild, short-lived febrile episodes in 26 and 23% of the recipients after the first doses of high- or low-titer vaccine, respectively, in comparison with 13% of the infants receiving the placebo. Febrile reactions occurred less frequently in vaccinees after the second or third dose than after the initial dose. The vaccine was not significantly associated with diarrhea or any additional symptom or sign. Serum specimens obtained shortly before the first, 4 weeks after the first, and 4 weeks after the third dose of vaccine or placebo were tested by an immunoglobulin A enzyme-linked immunosorbent assay and by neutralization assays. Seroresponses occurred significantly more often after 3 doses than after a single dose of either vaccine. Immunoglobulin A responses were observed in 80 and 79% of the infants after 3 doses of high- or low-titer vaccine, respectively. Most of the infants tested developed a neutralization response to RRV after 3 doses of the high- (90%) or low-(88%) titer vaccine. Neutralization response rates to human rotavirus serotypes 1 to 4 after 3 doses were similar in both vaccine and 87 of 90 receiving the high-titer vaccine developed seroresponses, as detected by any of the assays employed. The study indicates that 3 doses of quadrivalent vaccine at a titer of 10(6) PFU of each component offered no advantage over the lower-titer preparation for use in efficacy trials.
在委内瑞拉加拉加斯对302名婴儿进行的双盲研究中，我们评估了一种四价轮状病毒疫苗的反应原性和抗原性。该疫苗由3型恒河猴轮状病毒（RRV）以及RRV与人类D株的三种单基因替代重配株（D x RRV，1型）、DS1（DS1 x RRV，2型）或ST3（ST3 x RRV，4型）组成。分别向99名和101名婴儿接种了由每种成分10⁵ PFU（低滴度）或10⁶ PFU（高滴度）组成的三剂四价疫苗，从第二个月开始，每隔4周接种一次；102名婴儿接受了安慰剂。在接种疫苗后的一周内，每隔一天进行一次家访以监测接种后的反应。与接受安慰剂的婴儿中的13%相比，在接种第一剂高滴度或低滴度疫苗后，分别有26%和23%的接受者出现了轻度、短暂的发热发作。接种第二剂或第三剂疫苗后，发热反应的发生频率低于初次接种后。该疫苗与腹泻或任何其他症状或体征无显著关联。在接种第一剂疫苗前不久、接种第一剂疫苗后4周以及接种第三剂疫苗或安慰剂后4周采集的血清标本，通过免疫球蛋白A酶联免疫吸附测定和中和试验进行检测。接种三剂疫苗后出现血清反应的情况明显多于接种一剂疫苗后。接种三剂高滴度或低滴度疫苗后，分别有80%和79%的婴儿出现了免疫球蛋白A反应。在接种三剂高滴度（90%）或低滴度（88%）疫苗后，大多数接受检测的婴儿对RRV产生了中和反应。接种三剂后，疫苗对1至4型人类轮状病毒血清型的中和反应率相似，并且在接受高滴度疫苗的90名婴儿中，有87名通过所采用的任何一种检测方法检测出产生了血清反应。该研究表明，在疗效试验中，每剂成分滴度为10⁶ PFU的三剂四价疫苗并不比低滴度制剂更具优势。
