A single 15-mcg dose of a new hemagglutinin antigen without alum adjuvant conferred a protective immune response against novel influenza A (H1N1) vaccine in the majority of people aged 12-60 years, results from a randomized, placebo-controlled study demonstrated.

Developed by Hualan Biological Bacterin Co., the vaccine was recently approved for sale in China, reported the researchers, who conducted the clinical trial in Taizhou. The results were reported on Oct. 21 in the New England Journal of Medicine.

“An important method of controlling [the current H1N1] pandemic will be large-scale immunization,” wrote the researchers, who were led by Dr. Feng-Cai Zhu of the Jiangsu Provincial Center for Disease Control and Prevention in Nanjing. “Currently used trivalent seasonal-influenza vaccines are unlikely to provide protection against the new 2009 pandemic influenza A (H1N1) virus; hence, there is an urgent need to develop a vaccine against it.”

Dr. Zhu and associates developed a monovalent, split-virus vaccine prepared from reassortment vaccine virus A/California/7/2009 NYMC X-179A, which was distributed by the U.S. Centers for Disease Control and Prevention. It was produced for the study in embryonic chicken eggs according to the same standard methods that are used for the production of trivalent inactivated vaccine against seasonal influenza (N. Engl. J. Med. 2009 [doi:10.1056/NEJMoa0908535]).

Between July and August of 2009 the researchers enrolled 2,200 healthy subjects aged 3-77 years and randomized them to receive placebo; vaccine with adjuvant at doses of 7.5 mcg, 15 mcg, or 30 mcg; or vaccine without alum adjuvant at doses of 15 mcg or 30 mcg. Twenty one days later, 2,103 of the study participants (96%) received a second dose. Serologic analyses were performed at baseline, on day 21, and on day 35.

The researchers found that the proportion of study participants who achieved a hemagglutination-inhibition tier of 1:40 or more was highest in the group that received the 30-mcg dose of vaccine without adjuvant.

In the group that received the 15-mcg dose, a hemagglutination-inhibition tier of 1:40 or more was achieved by day 21 in 75% of study participants aged 3-11 years, 97% of those aged 12-17 years, 97% of those aged 18-60 years, and in 79% of those who were age 61 and older.

By day 35 – after the second dose – a hemagglutination-inhibition tier of 1:40 or more was achieved in 98% of study participants aged 3-11 years, 100% of those aged 12-17 years, 97% of those aged 18-60 years, and in 93% of those who were age 61 and older. The percentages were the same in the two younger groups and slightly higher in the two older groups for those receiving the 30-mcg dose, Dr. Zhu and associates wrote.

Injection site or systemic reactions characterized as “mostly mild in nature” occurred in 6%-16% of study participants; no serious adverse side effects associated with the vaccine were observed.

“Although one dose of 15 mcg of vaccine without adjuvant protects the majority of persons, another dose given 21 days later will increase the antibody response in children,” the researchers concluded. “The decision about whether to administer two doses of vaccine in children will need to be made by public health officials. One argument for a two-dose vaccine schedule in children is the unusual epidemiology of the 2009 H1N1 pandemic: it affects younger age groups, including young children, and significant morbidity and mortality appear to occur in these younger age groups.”

Hualan Biological Bacterin Co. supported the study. Of the 20 study authors cited, three are Hualan employees; the remainder disclosed no relevant conflicts of interest.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

一项随机安慰剂对照试验证实，在没有铝佐剂的情况下，单剂量15 µg的新型血凝素抗原可使12~60岁人群中的大多数人产生抗新型甲型H1N1流感的保护性免疫反应。

 

在泰州进行临床试验的研究人员报告说，该疫苗由华兰生物疫苗有限公司研发，最近获准在中国上市。10月21日的《新英格兰医学杂志》报告了试验结果。

 

由南京江苏省疾病预防控制中心的Feng-Cai Zhu博士领导的研究人员写道，“控制(目前H1N1)流行的重要方法是大规模免疫接种。”“目前使用的三价季节性流感疫苗不太可能提供抗2009年新型甲型H1N1流感病毒的保护作用，所以急需研发能对抗该病毒的疫苗。”

 

Zhu博士及其同事们采用来源于美国疾病预防控制中心的A/California/7/2009 NYMC X-179A重配病毒株研发出一种单价裂解疫苗。根据与三价灭活季节性流感疫苗相同的标准生产方法，其用于在鸡蛋胚胎中的研究(N. Engl. J. Med. 2009 [doi:10.1056/NEJMoa0908535])。

 

在2009年7月~8月间，2,200例年龄介于3~77岁的健康受试者被随机分组：安慰剂组；无佐剂疫苗7.5 µg、15 µg或30 µg组；或有铝佐剂的疫苗15 µg或30 µg组。21天后，2,103例参与者(96%)接受了第2剂疫苗或安慰剂。在基线、21天及35天时对患者进行血清学分析。

 

研究者发现，获得1:40或更高的血凝抑制滴度者在接受30 µg无佐剂疫苗组中最多。 

 

在接受15 µg剂量组，75%的3~11岁参与者，97%的12~17岁参与者、97%的18~60岁参与者以及79%的61岁以上参与者在21天时血凝抑制滴度达到1:40或更高。

 

Zhu博士及其同事写到，到35天时——接受了第2 剂安慰剂或疫苗后——98%的3~11岁参与者、100%的12~17岁参与者、97%的18~60岁参与者以及93%的61岁以上参与者血凝抑制滴度达到1:40或更高。对于那些接受30 µg剂量的群体，以上比例在2个较年轻组中相同，而在2个年龄较大组中略高。

 

6%~16%的研究参与者出现了定性为“通常轻度”的注射部位局部或全身反应。没有观察到与疫苗有关的严重不良反应。

 

“虽然单剂15 µg无佐剂疫苗可使大多数人产生保护性免疫反应，但是在21天时再次注射将增加儿童的抗体反应，”研究者总结道，是否需要为儿童注射2剂疫苗需要由公共卫生专员来决定。支持儿童2剂疫苗接种程序的一项依据是2009年H1N1流感不同寻常的流行：它影响包括儿童在内的年轻人群，而且似乎这些年轻人群中的患病率和病死率显著增加。”

 

华兰生物疫苗有限公司支持了该项研究。在所列举的20位研究作者中，3位为华兰雇员；其余作者均声明无相关的利益冲突。

 

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