Thread by @dariusdariusdar

The #COVID19 #vaccines are designed to prevent disease—they are also incredibly effective at preventing #transmission! Here we discuss the immunological mechs that cause vaccines to tangibly and effectively reduce transmission! 🧵 1/n sciencedirect.com/science/authSh… @TheLancetInfDis

Humbled to have put together a review on the COVID19 vaccines’ ability to reduce transmission with my fellow med skool classmates from @SpikeSupport- @CarolineNValdez, @Larson_HaleighT, @ChaneyKalinich, and mentored by the amazing @VirusesImmunity 2/n

We note four stages by which vaccine-induced immunity can ⬇️ transmission: 1️⃣ infection, 2️⃣ viral replication, 3️⃣ threshold for host-to-host spread, and 4️⃣ degree of symptomaticity 3/n

1️⃣Infection and 2️⃣replication are necessary stages before #SARS-CoV-2 has the capacity to transmit or cause symptoms 4/n

Stage 1️⃣- Infection: We define infection as when the virus 🦠 enters target cells. This step requires that the 🦠 lands in the respiratory mucosa👃 🫁 of a susceptible individual, the viral spike protein actively binding ACE2, and finally that the 🦠 infiltrates the cell 5/n

If any of these prereqs is not met, the virus does not infect. Thus, if a vaccine can prevent the spike from binding ACE2, the virus cannot infect 6/n

Vaccines prevent infection by making ⬆️ amounts of neutralizing antibodies (NAbs ✌️ ). NAbs✌️neutralize the infectivity of a virus by binding 🦠 spike protein, preventing its interaction with ACE2. All the SARS-CoV-2 vaxs are excellent at inducing neutralizing blood IgA & IgG 7/n

Unfortunately, the blood🩸is not where infection occurs. You get sneezed🤧 on, breathed👄on, coughed😷 on thru your respiratory mucosa 👃🫁. Therefore, stopping infection must also occur here. To prevent infection, one must have ⬆️ NAbs✌️present AT the site of exposure.👃🫁>🩸8/n

⬆️ levels of IgA (incl. dimeric) and IgG NAbs✌️are seen in saliva🤤 of those vaccinated with the mRNA vaccines (Moderna or Pfizer),... 9/n

https://twitter.com/ImmunoFever/status/1432418184867549185?s=20

but NOT in an adenovirus-vectored vaccine (i.e. J&J), despite high levels of blood🩸NAbs✌️in both types 10/n

https://twitter.com/ImmunoFever/status/1432418177913393154?s=20

This beautifully reiterates preclinical studies in rhesus macaques 🐒 showing ⬆️ level of IgA/IgG in respiratory tract 👃 🫁 with an mRNA vax (i.e. Moderna @KizzyPhD), but not with an adeno-vectored vax (i.e. AstraZeneca) 11/n

https://twitter.com/dariusdariusdar/status/1432468838201843714?s=20

Stage 2️⃣- Replication: If sterilizing NAbs✌️are insufficient to keep the virus from entering the cells, SARS-CoV-2 replicates, generating increased copy numbers within its host.
🦠 ➡️🦠🦠🦠🦠
Vaccines work strongly during this 2️⃣ replication stage as well! 12/n

Individuals fully vaccinated with Pfizer BioNTech, Moderna, and AstraZeneca limit mucosal 👃 🫁 viral loads by strongly inducing virus-specific serum IgG✌️, and CD8 and CD4 T cell activity. 13/n

https://twitter.com/EricTopol/status/1386368893132828674?s=20

Thus, these vaccine-induced immune mechanisms disrupt viral replication and prevent SARS-CoV-2 from reaching high enough levels to fully cause symptoms and/or transmit.
🦠 ➡️❌🙅‍♂️❌🦠🦠🦠🦠 14/n

Stage 3️⃣- ⬆️ the threshold for host-to-host spread: By keeping 🦠 levels low, vaccines ⬇️ the number of 🦠 particles that are emitted by infected individuals. 15/n

Nasopharyngeal 👃 viral load is a strong correlate for transmissibility potential. Vaccines ⬇️ the viral load, thereby ⬇️ infectivity of an infected individual. 16/n

https://twitter.com/erlichya/status/1421510747608297473?s=20

Additionally, breakthrough infections are ⬇️ infectious than unvaccinated individuals with similar viral loads,... 17/n

...possibly due to antibodies✌️from the vaccine that coat the virus which limit the infective capacity of coated viruses through complement or steric hindrance. 18/n
medrxiv.org/content/10.110…

Stage 4️⃣- ⬇️ of symptoms: SARS-CoV-2 vaccines are shown to drastically ⬇️ symptomatic 🤒 infection and severe COVID-19 in infected individuals. The result is that the modes for aerosolized 🦠particles to spread between individuals (coughing and sneezing 🤧) are reduced. 19/n

An index case who is asymptomatic is ⬇️ likely to infect contacts. PLUS, those infected by asymptomatic cases are ⬇️ likely to be symptomatic 20/n

https://twitter.com/LeoMarti_EpiTB/status/1429847148825300997?s=20

While SARS-CoV-2 viral loads are similar between symptomatic and asymptomatic individuals, ⬆️ 🦠 levels persist in symptomatic individuals for longer. Thus, vaccines may also ⬇️ the infectious period of infected individuals, further ⬇️ transmission. 21/n

https://twitter.com/RolandBakerIII/status/1421553132970995712?s=20

In all, vaccines reduce transmission by:
1️⃣- ⬇️ infection
2️⃣- ⬇️ viral replication
3️⃣- ⬆️ threshold for host-to-host transmission
4️⃣- ⬇️ symptomatic amplification of spread
22/n

Through these 4 mechanisms, many of the vaccines are quite effective. We compiled a comprehensive list (as of the beginning of July ’21) of clinical trials and real-world studies showing vaccine efficacies and effectiveness against asymptomatic infection and transmission. 23/n

The list is too long to post as a screenshot, so we are attaching them here 24/n ars.els-cdn.com/content/image/…

But the message is clear- the vaccines DEFINITELY provide moderate to excellent ability to 🚫prevent🚫 infection (80-90%). 25/n

A couple well-done studies go one step further and show vaccines prevent transmission AT LEAST 50% after one dose (so this is the very low estimate). The other study shows much higher prevention 26/n

https://twitter.com/EricTopol/status/1388993718741393411?s=20

Even in the uncertainty of delta, “waning immunity”, high community case rates, and high background unvaccinated infection, the vaccines are still quite effective. We provide a limited effectiveness table: 27/n

All the currently approved vaccines are intramuscular-injected vaccines. We speculate on the benefit of alt vaccine strategies, especially those targeting the mucosa👃🫁 -- the primary site of SARS-CoV-2 infection and replication. 28/n

A mucosal vaccination approach aims to 🛑 the virus directly at the site of infection by eliciting neutralizing IgA and IgG✌️ antibodies and resident T cells, slowing the virus at stages 1️⃣ and 2️⃣ 29/n

For example, in mice 🐁, the spray version of the AstraZeneca vax generates better mucosal👃🫁 IgA NAb ✌️and cell mediated immunity, and in rhesus macaques 🐒, this spray vax managed to completely prevent infection better than the injected vaccines. 30/n

https://twitter.com/danmucida/status/1296148651971096576?s=20

Fortunately, because they target the mucosal👃🫁 surfaces, these vaccines also have the benefit of being administered as a spray🚿 or a supplement 💊, avoiding the needle💉 31/n

We hope this review provides a good general framework for understanding the basic mechanisms for vaccine-mediated transmission prevention of #COVID19
Be proud of your immune system, which with the guide of the SARS-CoV-2 vaccines, can squash the virus in its tracks
32/n

Once again all the love in the world to @CarolineNValdez @Larson_HaleighT @ChaneyKalinich for persistently researching and writing this review with me, and for @VirusesImmunity for encouraging us to undertake this project and strongly 💪 guiding us along the way 33/33

Our list isn’t comprehensive— for some more comprehensive lists related to delta and variants (not necessarily just about infection), try @florian_krammer’s excellent “work in progress” or

https://twitter.com/thelancet/status/1437402964919001088?s=21

https://twitter.com/florian_krammer/status/1435688828698828804

I thought I shared the accessible link, but our manuscript is available to anyone temporarily open access here:
authors.elsevier.com/a/1dlF55E-UoV4…

https://twitter.com/dariusdariusdar/status/1438233635577008140