ATLANTA (EGMN) – New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.
And new vaccines are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” Dr. Bright told attendees at the International Conference on Emerging Infectious Diseases (ICEID 2010).
Current influenza vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization.
In addition, vaccine development is costly, complicated, and time consuming. As the recent H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.
He discussed three promising types of influenza vaccines: live attenuated influenza viruses (LAIV), recombinant viruslike particles (VLP), and plant-based production of vaccines. Each holds promise, but all involve significant challenges, including safety, immunogenicity, scalability, and regulatory issues.
LAIV: Innovative Yet Decades Old
LAIVs have been used to combat seasonal influenza for decades in some parts of the world, including the United States and Russia, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. In fact, he said, LAIV is the lowest-cost influenza vaccine available today. It’s easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, he said.
There are challenges, however. LAIV “doesn’t follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles.
Moreover, LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But, he added, some of those limitations are based on “unfounded fears of the risk of reassortment.”
Over the last few years, LAIV technology has expanded into development of both seasonal and pandemic vaccines.
VLP: Dealing With Vectors
VLP vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Dr. Bright explained that although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.
Animal and early clinical studies suggest a broad immune response, but low immunogenicity may be an issue, he said; VLPs may need adjuvants.
Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove – or demonstrate the safety of – the residual vectors, Dr. Bright said, noting that such concerns could lead to regulatory challenges.
Plant-Based Vaccines: Speedy Development
Plant-based vaccines have been advancing steadily since 2000, he reported. Such vaccines can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”
Safety appears to be less of a concern than it is for VLPs, according to Dr. Bright, because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. “It’s all in plants, so that implies a safe host cell system.” More research needs to be done, however. “There are many things we don’t know about the safety of plant-based proteins,” he cautioned.
Researchers are exploring the issue of low immunogenicity with plant-based vaccines, he said. Like the VLPs, plant-based vaccines will likely benefit from an adjuvant.
Dr. Bright disclosed receiving stock as part of a management position in 2006 from Novavax Inc.
Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
亚特兰大(EGMN)——作为全球性非盈利卫生组织，适宜卫生技术项目流感疫苗计划的科学主任Rick Bright博士说，新型流感疫苗的研发进度很快，目前处于各个阶段的不同技术大约有75种之多。
在国际新发传染病研讨会(ICEID 2010)上，Bright博士告知与会者，目前人们对新型疫苗的需求非常迫切：现有的季节性流感疫苗在年龄偏大的成年人中的有效率只能达到30%~50%，针对大流行病的候选疫苗“在临床研究中仅呈弱免疫原性”。
现有流感疫苗的安全性和免疫原性或许能够得到保障，但却极易受到抗原漂移和抗原转变的影响，而这会使其有效性大打折扣，从而需要重新形成抗体和反复接种。
此外，疫苗的研发成本很高、过程复杂且耗时很长。Bright博士说，正如最近一次H1N1流感疫情暴发所反映的问题，传统的生产过程难以应付这样的大流行病。
Bright博士对3种前景看好的流感疫苗进行了讨论：流感病毒活疫苗(LAIV)、重组病毒样颗粒(VLP)和植物疫苗的生产。这几种疫苗的前景都很乐观，但也都面临重大挑战，包括安全性、免疫原性、大规模生产的可行性以及法规问题。
LAIV：虽然已有几十年的历史但仍属创新型疫苗
在包括美国和俄罗斯在内的部分国家和地区，LAIV用于对抗季节性流感已有几十年的历史，但Bright博士仍将其称为创新型疫苗。尽管这类疫苗的安全记录很好，成本也较低，但尚未得以公认或广泛使用。Bright博士说，事实上，LAIV是现有的成本最低的一种流感疫苗。其生产和提纯的难度都不大；能够产生广泛的免疫应答，包括一定的黏膜和细胞免疫性；并且对于从未接种过的人群也有效。
但LAIV也面临着一些挑战。LAIV“并不遵循已知的、已经确立的免疫相关性”，这可能导致法规和许可申请方面的障碍。
而且，LAIV对于已经接种过的成年人效果不佳，目前在用于儿童和部分高危人群时也有一定的局限性。Bright博士补充道，但这些局限性有一部分是基于“对病毒重配风险的无谓担忧”。
在过去几年内，LAIV技术已被用于季节性流感和大流行性流感疫苗的研发。
VLP：需解决病毒载体问题
Bright博士说，目前处于研发早期的VLP疫苗已有许多种，由于这类疫苗成本低、产出高、生产周期短(12周)，因而前景看好。Bright博士解释道，虽然VLP含有多种类似于病毒体的流感蛋白，但却不含任何遗传物质，因此不能复制或引发感染。
Bright博士说，动物研究和早期临床研究表明，这类疫苗能够产生广泛的免疫应答，但免疫原性低可能是一大问题；VLP可能需要使用佐剂。
Bright博士说，由于所有的VLP都是“依赖一些病毒载体”，因此安全性也是一大问题。目前的挑战是如何去除残余的载体，或证明这些载体是安全的。Bright博士指出，这些担忧可能会带来法规监管上的挑战。
植物疫苗：研发进度很快
Bright博士报告称，自2000年以来，植物疫苗的研发一直呈现出稳步进展的势头。这类疫苗的生产周期很短，从序列分析到释放大约只需要8周。植物表达的新途径实现了高产出、低生产成本。Bright博士说，此外，这种新途径“可以与不断新增的菌株混合且匹配。”
Bright博士说，较之VLP，植物疫苗的安全性问题不大，因为这类疫苗不含任何动物细胞、微生物病原体或动物病毒。“植物疫苗均取材于植物，这意味着其宿主细胞系统是安全的。”不过，仍需开展更多的研究以证实其安全性。Bright博士提醒道：“对于植物疫苗的安全性，还有很多事情是我们所不知道的。”
Bright博士说，目前研究者正在探讨植物疫苗的低免疫原性问题。和VLP一样，使用佐剂对植物疫苗很可能也有益处。
Bright博士声明曾于2006年因其管理职位接受了Novavax公司的部分股份。
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