A lot of people have asked me what's the harm in just skipping safety and efficacy vaccine trials and getting vaccine candidates out to the general public right away. Last week @VirusesImmunity has a cautionary tale about what can happen when vaccines go wrong https://twitter.com/VirusesImmunity/status/1243997325804142593

This study looked at IgG (antibodies) induced by a SARS classic vaccine made with modified vaccinia Ankara (MVA). This is a strain of cowpox virus that expresses the Spike protein from SARS classic. MVA usually causes a mild infection that can induce immune responses.

Fun vaccinology fact: the term "vaccine" comes from "vaccinia", which is the scientific name for cowpox virus. Vaccinia virus has been used for centuries to immunize people against smallpox because cross-reactive immunity against vaccinia protects against variola (smallpox) virus

TECHNICALLY "vaccination" only refers to immunization with vaccinia virus, although the word has evolved to refer to any type of protective immunization. In this case, it actually IS vaccination because this uses MVA to induce the immune system to produce antibodies against Spike

Anyway, Dr. Iwasaki's thread covers the scientific findings in great detail. READ IT! The key take-home message is that the antibodies induced by MVA-Spike itself caused more severe lung injury by altering the way certain cells (alveolar macrophages) respond to infection.

The anti-Spike IgG induced by this vaccine appears to make these macrophages overwhelmingly proinflammatory--meaning they secrete cytokines (proteins that cells use to communicate with each other and coordinate immune responses) that promote inflammation.

Inflammation is important for responding to and clearing viral infections. However, that process is tightly regulated. When inflammation occurs in an unregulated way, it can cause tremendous damage. In this case, it appears to damage the lung tissue directly.

I can't think of any exceptions to the rule that severe viral diseases are a consequence of unchecked inflammation. Ebola, Lassa, highly pathogenic flu (1918/H1N1), SARS classic, MERS-CoV...ALL of these are lethal because inflammation gets completely out of control.

My research focuses on understanding these host responses and the fine line between protective and pathogenic responses. My work on #SARSCoV2 aims to investigate this same question in animal models. I suspect we'll see similar inflammatory response disruption in severe #COVID19.

It's thus essential that we test vaccines against #SARSCoV2 for safety because of this possibility. Widespread distribution of a vaccine that generates IgG responses that can actually make #COVID19 WORSE would be disastrous. It would be a cost measured in lives.

There are other examples of vaccine candidates failing spectacularly and increasing disease risk. The infamous STEP trial tested a promising adenovirus-based HIV vaccine. It failed, as it evidently increased risk of HIV infection.
https://rupress.org/jem/article-lookup/doi/10.1084/jem.20072681

We don't know much about #SARSCoV2 and it will be absolutely critical to make sure that any vaccine will be safe and effective. Please read Dr. Iwasaki's excellent and thoughtful thread explaining this paper in detail--a great example of #scicomm on something relevant to us all.

OH and if you want a great source of expertise on macrophages and their role in host responses to viral infection and pathogenesis, follow my collaborator and very dear friend, @DrJuliet5. She's a master of macrophage biology, particularly in emerging respiratory pathogens.