Hensley Lab Profile picture
Nov 25 12 tweets 6 min read
We developed a new multivalent mRNA vaccine against all known influenza virus subtypes. Our study describing the vaccine was just published in @ScienceMagazine. 1/n
science.org/doi/10.1126/sc…
We created an mRNA vaccine expressing HAs from all 20 flu types. First, we vaccinated mice and found that this multivalent vaccine elicits robust antibody responses reactive to every HA. 2/n
Our new vaccine does not simply elicit antibodies that cross-react to every known influenza subtype. Instead, we found that that the vaccine elicits distinct antibody lineages against all 20 different flu HAs. 3/n
The vaccine elicits both neutralizing and non-neutralizing antibodies against diverse influenza subtypes with pandemic potential. 4/n
The vaccine protected mice against viruses that were similar to the vaccine components. But more importantly, the vaccine prevented severe disease and death against viruses that were distinct from the vaccine components. This resembles a pandemic situation. 5/n
And that is our goal: to elicit a baseline level of immunity in the population that would not necessarily prevent infections with new pandemic strains--but rather prevent severe disease and death caused by new pandemic strains. 6/n
Here is an important part: we found that our vaccine elicits strong antibody responses in animals with and without prior flu exposures. We think that this vaccine has the potential to elicit responses in children, as well as the rest of us who have already encountered flu. 7/n
We found very similar results in ferrets. The vaccine elicited antibodies against all 20 HA components and protected animals from an antigenically distinct viral strain. Thanks to @Lakdawala_Lab and @SageVle
for completing ferret experiments. 8/n
We are now testing the vaccine in non-human primates and planning phase 1 human studies. We think this vaccine has the potential to elicit immunity that could be quickly recalled to significantly reduce severe disease and death from our next flu pandemic. 9/n
We've been working on this multivalent mRNA flu vaccine for years--most of this work was completed before the COVID pandemic. I'm grateful to work with the brilliant @WeissmanLab, and I'm so happy to see how mRNA vaccines proved to be so useful during the COVID pandemic. 10/n
Last but not least, I want to acknowledge my lab--especially @pennbgs @IGGPenn graduate student, Claudia Arevalo, who completed most of the experiments for this study. I also acknowledge @NIH, @CEIRRNetwork, and @PennMedicine for their support. 11/n
Thank you @akelvinlab for writing such a nice perspective of our study. 12/n
science.org/doi/10.1126/sc…

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More from @SCOTTeHENSLEY

Sep 29
@biorxivpreprint just posted our new manuscript showing that IgG3 antibodies are much better than IgG1 antibodies at recognizing flu and SARS-CoV-2 variants. This is a story of basic research having immediate clinical implications. (1/8)

biorxiv.org/content/10.110…
We started by cloning a bunch of flu antibodies that had the same variable domain with different constant domains. Conventional wisdom says that antibody constant domains do not affect antigen recognition. (2/8)
Consistent with conventional wisdom, when we tested binding of these antibodies to influenza HA, we found very little differences in binding (check out all of those 'ns')...but that is not the whole story.... (3/8)
Read 8 tweets
Jun 17
This is a really interesting paper tracking Omicron immune response in health care workers with different SARS2 exposures. This is an amazing cohort and great study but I disagree with some of the conclusions of the paper... 1/7

science.org/doi/10.1126/sc…
The most interesting data in the paper are in Figure 4. This figure includes samples from HCWs infected with Omicron who were (pink) or were not (black) previously infected with the original strain of SARS2. All of these people were vaccinated 3 times with an mRNA vaccine. 2/7 Image
Results from Figure 4: Individuals with prior SARS2 infection who were then infected with Omicron had a boost in N Abs. This is expected since the N protein hasn't changed much. But these individuals did not have a great spike Ab response (for example, RBD below). 3/7 ImageImage
Read 7 tweets
May 31
Our @CEIRRNetwork funded study reporting an H3N2 antigenic mismatch during the 2021-2022 Northern Hemisphere season was published today @CellReports. This provides an immunological explanation for the ineffectiveness of this year’s flu vaccine.
1 of 4
cell.com/cell-reports/f…
Thank goodness for preprints. We were able to make these data public via @medrxivpreprint in mid-December before H3N2 took off.
2 of 4
H3N2 activity remains unseasonably high in the United States and is taking off in other parts of the world.
3 of 4
Read 4 tweets
Dec 16, 2021
Unfortunately, there will likely be an H3N2 antigenic mismatch with the 2021-2022 Northern Hemisphere influenza vaccine. Our manuscript describing this has been posted on @medrxivpreprint. 1/10
medrxiv.org/content/10.110…
Influenza viruses have circulated at low levels during the COVID-19 pandemic, and population immunity against these viruses is low. As COVID-19-related restrictions are eased or lifted, we expect wide circulation of influenza viruses. 2/10
In recent weeks, a unique H3N2 clade, 3C.2a1b.2a2 (herein 2a2), has circulated at elevated levels in the United States and other parts of the world. 3/10
Read 11 tweets
Nov 19, 2021
I’m a scientist and I have 2 kids that are between 5 and 11 years old. I respect that some parents have concerns about COVID-19 mRNA vaccines for their young children. Here is a short thread why my wife and I decided to vaccinate both of our kids last week. (1/8)
A lot of my thoughts have been captured by my great colleagues Jeff Gerber and @DrPaulOffit from CHOP in this short editorial published yesterday in Science. Please read this if you haven’t already: (2/8)
science.org/doi/10.1126/sc…
As a society, we will eventually need to realize that all of us will be exposed to SARS-CoV-2 sometime during the next few years. The virus will continue to circulate and there is no escaping it unless you do not interact with humans. (3/8)
Read 8 tweets
Oct 2, 2021
Check out our new preprint: SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations
1/
medrxiv.org/content/10.110…
We found that both SARS-CoV-2 infections and mRNA vaccinations elicit antibodies that bind to the S1 and S2 regions of the SARS-CoV-2 spike. 2nd doses of vaccine primarily boost antibodies reactive to S1.
2/
Here is where it gets interesting: SARS-CoV-2 infections boost antibodies that react to the S2 region of OC43 (a related seasonal coronavirus). SARS-CoV-2 mRNA vaccines boost OC43-reactive antibodies less than infection.
3/
Read 11 tweets

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