【論文 開発中のSARS-CoV-2ワクチン】と【日経記事 新型コロナのワクチンは「パンドラの箱」か】(2020.10.2作成)

Noguchi Akio @Derive_ip

新型コロナのワクチン開発に関するレビュー論文が出ています。まだ、部分的にしか読んでいないですが、色々と勉強になりました。 nature.com/articles/s4158…

Noguchi Akio @Derive_ip

上記レビュー論文の筆者自身が論文の解説をしてくれているのでですが、なんと１３８ツイートのロングスレッド。もう、本編を読んじゃっても同じかも。 twitter.com/florian_kramme…

Florian Krammer @florian_krammer

1) SARS-CoV-2 Vaccines - I promised a Tweetorial and here we go. This is going to be long and nerdy. But I'll make sure it is easy to understand. If you want more details, please just read this: nature.com/articles/s4158…

2020-09-28 09:14:36

Noguchi Akio @Derive_ip

この手の情報は分科会メンバーからのリークではなく、政府から正式に周知させるべきだと思いますが、「コロナのワクチンは実現しても当初は重症化を防ぐだけで、感染や発症を予防できるかは別問題」とのことです。 nikkei.com/article/DGXMZO…

Noguchi Akio @Derive_ip

実は、現在開発されている(政府が調達している)ワクチンは、感染予防効果を十分に得られない可能性が高いタイプのワクチンらしいのです。この点は、先日紹介したワクチンのレビュー論文に書いてありました。 twitter.com/Derive_ip/stat…

Noguchi Akio @Derive_ip

そもそも若い世代は重症化する可能性は低いので、重症化予防しかないワクチンを接種するメリットがどれだけあるのでしょう？しかもそれでいて、副反応のリスクもあり、重症化しなくても後遺症が残る可能性があるなら、若い世代は積極的に接種したいとは思えないのではないでしょうか？

Florian Krammer @florian_krammer

1) SARS-CoV-2 Vaccines - I promised a Tweetorial and here we go. This is going to be long and nerdy. But I'll make sure it is easy to understand. If you want more details, please just read this: nature.com/articles/s4158…

Florian Krammer @florian_krammer

2) I'll try to give an overview of the process, the technologies, correlates of protection, the candidates, how they perform in non-human primates and what we know about their performance in humans so far.

Florian Krammer @florian_krammer

3) Let's start with the process. Developing vaccines usually takes a long time. Usually there is a medical need and some idea of how to design the vaccine, often in an academic lab. Versions of the vaccine are tested in iterative processes, the constructs are optimized....

Florian Krammer @florian_krammer

4)....and this can take a few years. Then funding needs to be secured/a commercial partner needs to be found to advance this further into clinical trials. This can also take time. Once funding is in, a process is developed, GMP (good manufacturing practice aka high quality)....

Florian Krammer @florian_krammer

5)...material needs to be produced, more formal animal experiments and toxicology studies are performed and then an IND (investigational new drug) application is filed. This process might take another 2-4 years. Then you go into Phase I trials (2 years), Phase II trials.....

Florian Krammer @florian_krammer

6)...(2 years) and if everything looks great, the market is still there and the developer is sure the risk is low, they embarke on Phase III (which takes also about 2 years and is very very expensive). Just to explain the Phases: Phase 1 (<100 individuals) to check initial safety

Florian Krammer @florian_krammer

7) and some immunogenicity, Phase II (a few 100 individuals) explores safety, immunogenicity and optimizes doses/regimens and Phase III (often thousands of individuals) looks at how well the vaccine works (efficacy) and safety in a large number of people.

Florian Krammer @florian_krammer

8) Now, if Phase III looks good you file a biologics license application (BLA) to the FDA to bring the vaccine to the market. They may ask for more data, it is a process. You end up with about 15 years of development. Only then you start to produce the vaccine, which is expensive

Florian Krammer @florian_krammer

9) Here is an overview of the process. pic.twitter.com/yncorVhxe9

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Florian Krammer @florian_krammer

10) Now, for SARS-CoV-2 this looks very different. A lot of preclinical work was done on coronavirus vaccines. The target, the spike protein was known. So, the fiddling around for years was skipped. This antigen was then just plugged into existing technology.....

Florian Krammer @florian_krammer

11) ...and existing processes. In some cases, preclinical/toxicology data from similar vaccines was used for the initial IND. Clinical phases were staggered - which speeds thing up a lot.

Florian Krammer @florian_krammer

12) Now, the question is, doesn't this compromise safety? Not really. Vaccine development is slow because it needs to be de-risked. You only go to the next step if you think the risk of failure - which will costs lots of money - is low. For SARS-CoV-2 money doesn't matter.

Florian Krammer @florian_krammer

13) Everything is done at economic risk - and that speeds things up. No sane vaccine developer would do this in 'peace time'. So, we are already in Phase III trials, what happens next? Now, vaccines can be licensed the regular way or via an 'emergency use authorization'.

Florian Krammer @florian_krammer

14) The 'emergency use authorization' allows the vaccine to be used before it is fully licensed based on available data that suggests a risk benefit. It is unclear if this will happen with SARS-CoV-2 vaccines, but it is possible. We will see.

Florian Krammer @florian_krammer

15) The FDA published a guidance document for SARS-CoV-2 vaccine developers if you are interested. It can be found here. fda.gov/media/139638/d…

Florian Krammer @florian_krammer

16) So, with considering all this, we end up with a vaccine development timeline of about 10 months to 1.5 years - depending on the licensing pathway. pic.twitter.com/9iGdxaEkjM

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Florian Krammer @florian_krammer

17) We will get back at what will happen once we have a licensed vaccine. But let me now go into the different types of vaccines that are around. We talk about 'vaccine platforms' when we talk about different kinds of vaccines. Currently, more than 180 vaccines are...