婴儿对人轮状病毒G1型候选疫苗重配株WI79-9的免疫反应：对病毒表面蛋白VP7和VP4的不同剂量反应模式。

Infant immune response to human rotavirus serotype G1 vaccine candidate reassortant WI79-9: different dose response patterns to virus surface proteins VP7 and VP4.

作者信息

Clark H Fred, Lawley Diane, Shrager Dorothy, Jean-Guillaume Danielle, Offit Paul A, Whang Soo Yeon, Eiden Joseph J, Bennett Philips S, Kaplan Karen M, Shaw Alan R

机构信息

Division of Immunologic and Infectious Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

出版信息

Pediatr Infect Dis J. 2004 Mar;23(3):206-11. doi: 10.1097/01.inf.0000115503.55212.bf.

DOI:10.1097/01.inf.0000115503.55212.bf

PMID:15014293

Abstract

BACKGROUND

Rotavirus is the leading cause of morbidity from gastroenteritis in the developed world and the leading cause of mortality from viral gastroenteritis (estimated 600000 deaths) worldwide. G1 is the most prevalent human serotype. Reassortant rotavirus between simian rotavirus RRV or bovine rotavirus WC3 and human strain rotaviruses have been extensively tested as candidate vaccines. Rotavirus (RV) reassortant strain WI79-9 consists of a human (strain WI79) G1 serotype VP7 surface protein on a bovine (strain WC3) background. It is a key component of a pentavalent (G1, G2, G3, G4 and P1) WC3 reassortant vaccine candidate, RotaTeq, now being tested in Phase III clinical trials.

METHODS

We studied 84 infants between the ages of 2 and 8 months who received 3 oral doses of WI79-9. Serum neutralizing antibody was measured to the human (WI79 serotype P1 G1) and bovine (WC3 serotype P7 G6) parent RV after each dose. A significant response was defined as a > or =3-fold rise in antibody titer between the predose and postdose sera.

RESULTS

In two separate cohorts of vaccinees given three doses of WI79-9 reassortant rotavirus, 68 to 75% of infants demonstrated a significant response to WC3 (VP4, P7) after Dose 1, fewer (24 to 39%) responses were detected after Dose 2 and rare (0 to 4%) additional responses occurred after Dose 3. The cumulative response rate to WC3 after three doses was 95% in both trials. In contrast 23 to 37% had a significant response to WI79 (VP7, G1) after Dose 1, and 57 to 61% had a significant response after Dose 2. Additional significant responses after Dose 3 led to a cumulative response of 70 to 84%.

CONCLUSION

Two doses of G1 reassortant WI79 were necessary to induce significant antibody responses to human G1 (VP7) antigen in >50% of infants. Three doses were required to achieve significant antibody responses to VP7 in >70% of infants.

摘要

背景

轮状病毒是发达国家中引起肠胃炎发病的主要原因，也是全球病毒性肠胃炎致死的主要原因（估计有60万例死亡）。G1是最常见的人类血清型。猿猴轮状病毒RRV或牛轮状病毒WC3与人类轮状病毒株之间的重配轮状病毒已作为候选疫苗进行了广泛测试。轮状病毒（RV）重配株WI79-9由牛（WC3株）背景上的人（WI79株）G1血清型VP7表面蛋白组成。它是一种五价（G1、G2、G3、G4和P1）WC3重配候选疫苗RotaTeq的关键成分，目前正在进行III期临床试验。

方法

我们研究了84名年龄在2至8个月之间的婴儿，他们口服了3剂WI79-9。每次给药后，检测血清对人（WI79血清型P1 G1）和牛（WC3血清型P7 G6）亲本RV的中和抗体。显著反应定义为给药前和给药后血清之间抗体滴度升高≥3倍。

结果

在两个分别接受三剂WI79-9重配轮状病毒的疫苗接种队列中，68%至75%的婴儿在第1剂后对WC3（VP4，P7）表现出显著反应，第2剂后检测到的反应较少（24%至39%），第3剂后出现的额外反应很少（0%至4%）。在两项试验中，三剂后对WC3的累积反应率均为95%。相比之下，23%至37%的婴儿在第1剂后对WI79（VP7，G1）有显著反应，第2剂后57%至61%的婴儿有显著反应。第3剂后的额外显著反应导致累积反应率达到70%至84%。