【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)

Florian Krammer @florian_krammer

118) All frontrunners and most of the >180 vaccines in the pipeline are given intramuscularly/as injected vaccines. This route is good to induce IgG which is prevalent in the lower respiratory tract and helps to protect the lung, which is great.

Florian Krammer @florian_krammer

119) However, these injected vaccines are poor inducers of mucosal antibodies in the upper respiratory tract which is mostly protected by secretory IgA1. This might lead to immunity that protects the lung (mild/no disease) but still allows for infection and potentially for...

Florian Krammer @florian_krammer

120)...onward transmission of the virus. Natural infection or live attenuated vaccines induce mucosal immunity and live attenuated vaccines might be much better in inducing sterilizing immunity in the upper respiratory tract. By not developing live attenuated vaccines we.... pic.twitter.com/UWTwiGLevo

拡大

Florian Krammer @florian_krammer

121) might end up with vaccines that protect us from disease but not infection and we might still be able to pass on the virus to others. This has been observed e.g. for influenza virus vaccines. Cool paper by @VivianaSimonLab about this below medrxiv.org/content/10.110…

Florian Krammer @florian_krammer

122) The next issue is old people. Old people usually don't respond well to vaccines, as can be seen in the Sinovac and Pfizer trials. We also know this from flu. There are even special formulations of flu vaccines for old people that make them respond better. In addition,

Florian Krammer @florian_krammer

123) it has even been shown that old people need much higher neutralizing titers than young people to be protected (again, for flu). So, the most vulnerable might profit the least from vaccines and we might needs special regimens or dosages for them.

Florian Krammer @florian_krammer

124) The next issue are kids. Many vaccines that are far in the pipeline (AZ, Moderna, Pfizer) show high reactivity including fever in adults. Children usually respond worse than adults and some of these first vaccines might not be tolerable in children.

Florian Krammer @florian_krammer

125) It is also entirely possible that the initial vaccines are effective and will be widely used but will then be replaced over time by vaccines that are as effective but less reactogenic.

Florian Krammer @florian_krammer

126) We also have no clue how long vaccine induced immunity will last. For natural infection, we seem to see a relatively normal immune response. Vaccine induced immunity might be shorter or longer lived. If it is short lived, it would still be OK since booster doses can be

Florian Krammer @florian_krammer

127) given. In fact, booster doses every few years are given for many vaccines, so I do not see this as an issue.

Florian Krammer @florian_krammer

128) Another problem is doses needed. It is very unlikely, that one dose is enough. Given the current global population, this means we need 16 billion doses if two shots are needed. It is impossible for one vaccine producer to make that much vaccine. This is the reason why...

Florian Krammer @florian_krammer

129) I am very happy that so many different vaccines and in so many geographic region are moving forward. This is the only way the demand can be met. Even then we might run into issues due to shortages of trivial things like glass vials, rubber stoppers or syringes.

Florian Krammer @florian_krammer

130) Also, many of us have a 'Western' view on SARS-CoV-2 vaccines. It is very likely that vaccines from China, India and others will satisfy the global demand, not US or European companies. Currently, it is even hard to imagine how Moderna's or Pfizer's vaccines could be....

Florian Krammer @florian_krammer

131) distributed in low and middle income countries given that they need to be stored frozen. Even within countries, it is often not clear yet, how vaccines will be distributed and who will get them first. The NAS has recently published a working document on this for the US....

Florian Krammer @florian_krammer

132)...which can be found here: nationalacademies.org/our-work/a-fra…

Florian Krammer @florian_krammer

133) And even if every vaccine now in advanced trials works and is churned out at full capacity, it will still take years to vaccinate the majority of the global population (I am not even taking vaccine hesitancy into account here).

Florian Krammer @florian_krammer

134) Despite all the challenges discussed here, we are in the process of developing vaccines as a countermeasure against SARS-CoV-2 at an unprecedented speed, and it is certainly possible that vaccines with safety and efficacy that has been proven in phase III trials....

Florian Krammer @florian_krammer

135).... might enter the market in 2020. Maybe initially not in large numbers and just for high risk groups but it will be a start. And every day after that will bring us closer to our normal way of living. I am very positive about this, we can do it!

Florian Krammer @florian_krammer

136) PS: There was an important question about safety post licensure. This is normal now and is called Phase IV. Safety will be monitored even after the vaccine is on the market. This allows to find rare side effects.

Florian Krammer @florian_krammer

137) PPS: Again, this is based on a review I recently wrote. Read that if you need more infos or refs. nature.com/articles/s4158…

Florian Krammer @florian_krammer

138) OK, somebody is going to ask which vaccine I would take. After seeing all the human data I would likely go with Pfizer or Novavax. But that might change, based on data coming up from Phase III trial. I am also kinda curious about Sanofi.