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An Update on Nasal Vaccines

Nasal vaccines are more likely to stop infection than vaccines injected into muscle because they stimulate mucosal immunity in the nose and respiratory system, the first line of attack, and they are likely to increase uptake especially among people with trypanophobia. Hence my longstanding call for an Operation Warp Speed for nasal vaccines. We haven’t got OWS 2.0 in the United States but nasal vaccines have recently been approved in China and India.

The Chinese vaccine is developed by CanSino and is the same as its injected vaccine but packaged in an aerosol taken with a nebulizer. It has been approved in China as a booster. Another advantage is that the Chinese nasal vaccine it’s one-fifth the dose of the injected version. India has also just approved a nasal vaccine on an emergency use basis. The Indian vaccine was developed by Bharat Biotech in a partnership with Washington University St. Louis.

Nasal vaccines as boosters seem like an especially promising approach as administration is much easier.

An Operation Warp Speed for Nasal Vaccines

I have been pushing for more funding for nasal vaccines since early last year when I wrote about trypanophobia and see also my Congressional testimony. The Washington Post reports that the idea is gaining traction among scientists but funding is limited:

As the omicron variant of the coronavirus moved lightning-fast around the world, it revealed an unsettling truth. The virus had gained a stunning ability to infect people, jumping from one person’s nose to the next. Cases soared this winter, even among vaccinated people.

That is leading scientists to rethink their strategy about the best way to fight future variants, by aiming for a higher level of protection: blocking infections altogether. If they succeed, the next vaccine could be a nasal spray.

…Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority — known as BARDA — are vetting an array of next-generation vaccine concepts, including those that trigger mucosal immunity and could halt transmission. The process is similar to the one used to prioritize candidates for billions of dollars of investment through the original Operation Warp Speed program. But there’s a catch.

“We could Operation Warp Speed the next-generation mucosal vaccines, but we don’t have funding to do it,” said Karin Bok, director of Pandemic Preparedness and Emergency Response at the National Institute of Allergy and Infectious Diseases. “We’re doing everything we can to get ready … just to get ready in case we have resources available.”

In my estimation, Operation Warp Speed was the highest benefit to cost ratio of any government program since the Manhattan Project. Amazingly, despite having now seen the benefits of the program and the costs of the pandemic, a government that spends trillions every year can’t get behind millions for a nasal vaccine.

To be sure, the emergency is over. The risk to the vaccinated are now tolerable and the benefits of further investment are much less than before vaccines were available. But the costs are also lower. Much of the research on nasal vaccines has already been done–what is needed is funding for clinical trials.

A nasal COVID vaccine will also pay off in future vaccine programs. If in a future pandemic we were able to use nasal vaccines to vaccinate more quickly, that alone could save many lives.

Addendum: Here’s my post on RadVac the do it yourself nasal vaccine.

Operation Warp Speed Should Not have Been Disbanded

Operation Warp Speed produced a new vaccine for a novel virus in record time but when Operation Warp Speed was disbanded by the Biden administration, vaccine research and development slowed from warp speed to impulse power. It’s ridiculous that it is taking longer to develop and deploy tweaks to the mRNA vaccines to deal with new variants than it took to develop the original vaccines from scratch. By the time we get an Omicron-specific vaccine that variant will have disappeared. This is no way to run a civilization.

We should be investing in a universal vaccine for all sarbecoviruses (of which SARS-COV-II is a member) and, as I have long argued (and here) a nasal vaccine. We need not exaggerate, for the vaccinated the dangers are no longer acute, but we should be better prepared for future variants and the savings from less sickness alone easily trump the costs. Indeed, the issue isn’t even so much the cost as the need to coordinate regulatory agencies, as OWS did, to speed approvals and reduce bureaucracy.

Patrick Collison, writing at Slow Boring, has the details (as Tyler also noted):

Despite excellent technology and promising early results in animal models, we estimate that the very earliest we will have access to these vaccines in humans is 2024. These groups need to run primate trials, then run human clinical trials, and then ramp manufacturing and distribution. Beyond having to jump through a lot of hoops, we’ve observed that they’re frequently tripped up by stupid things outside of their control, any one of which may hold their work back by months. (One group’s monkeys have been delayed by US Customs, which will push the start of their primate trial back ‘till September. Another is struggling to obtain necessary adjuvants. Multiple groups are unable to get access to current mRNA vaccines for research purposes because of legal barriers.) All groups we’ve interacted with are underfunded compared to what would be ideal.

Broadly speaking, the holdups involve some combination of logistical challenges and regulatory requirements, and the intersection between both. (You don’t in principle have to run a primate trial, but the FDA makes it harder to run a human trial if you don’t. You don’t in principle need to use “acute infection” as a trial endpoint; you could also use neutralizing antibody titers, which would be much faster and simpler.)

To speed things up:

  • We should lower the barrier for human clinical trials and use simpler endpoints. For many vaccine candidates, we could run human trials concurrent with primate trials (once basic safety data has been obtained). In humans, we don’t need to repeat Phase I trials for platforms that have already been validated and derisked. (In this vein, the FDA’s recent announcement about not requiring trials for updated platforms was encouraging.)
  • We should help these groups to scale manufacturing faster. Operation Warp Speed itself cost $10 billion; a second incarnation, with a tenth of that budget, could almost certainly accomplish a great deal.

…In our view it is probably true that, with competent execution, we could roll out pan-variant COVID vaccines before the end of 2022. Actually making that happen would require significant and coordinated logistical, regulatory, and administrative action. However, it would by no means be impossible. Not having pan-variant vaccines in 2022 is best thought of as a choice.

Let’s eliminate the Covid test entry requirement for the U.S.

That is the topic of my latest Bloomberg column, you ought to be able to guess most of my arguments.  Here is the very end:

I am not arguing for passivity in the face of danger. It is distressing that US policymakers do not seem interested in spending big for pandemic preparedness. America needs a new Operation Warp Speed for pan-coronavirus vaccines and nasal spray vaccines. It should be gathering more data on Covid and improving its system of clinical trials for anti-Covid remedies, among other measures.

I am simply saying that removing the Covid test for entry to the US would bring an end to one of the more egregious instances of “hygiene theater.” And it would send a signal that America is welcoming the world once again.

Recommended.  And note that the most responsible European countries do not impose such tests.

Sunday assorted links

1. MIE: “For $995, Love Cloud will fly you and a partner in a private airplane for 45 minutes so that you can have sex.”  (NYT)

2. What is working in Panama.

3. Is the hotel minibar disappearing?

4. Nasal vaccines (NYT).

5. Tim Harford’s ten best books for thinking about numbers and statistics.

6. The debate at the time as to whether Ukraine should have given up nuclear weapons (NYT).

7. MIE: First Norwegian salmon vending machine.

8. Claims about Ottawa, also reflecting “context is that which is scarce.”

Monday assorted links

1. More new views of Glen Weyl.

2. “Workplace premiums associated with teams of professionals have increased, while premiums for previously high-paid blue-collar workers have been cut.

3. A thread against molnupiravir.

4. “We find that a polygenic score capturing individuals’ genetic propensity to acquire education is significantly related to [voter] turnout.

5. Tom Holland to play Fred Astaire.  Can this be a good idea?

6. The recent trend in inflationary expectations.

7. Zvi summarizes Omicron.

Response to Questions from Senator Ted Cruz on Vaccine Passports

In my Congressional testimony I got into a little back and forth with Senator Ted Cruz on vaccine passports. Subsequently, I was asked to respond to a series of follow-up questions of the form:

If a vaccine passport or any other type of vaccine credential is required by individual private companies, do you have any concerns with a [educational institution/airline/grocery store…] refusing service or otherwise discriminating against an individual that:

(a) chooses not to receive the vaccine?
(b) is not a suitable candidate to receive the vaccine for medical reasons?

My response:

During the pandemic it was common for bars and restaurants, churches, gyms, shopping malls, entertainment venues, schools and universities and even parks and beaches in the United States to be closed for everyone. Similarly, international travel has been severely restricted for everyone. I think it an improvement to move from closed-for-all to open-for-some. Thus vaccine passports represent a lifting of restrictions and an increase in freedom on the path back to normality. Greece, for example, is scheduled to open to anyone with a record of vaccination, negative COVID test, or previous infection. This is good for Greece which relies on tourist revenues for a significant share of its economy and good for the world who want to visit sunny beaches and ancient ruins.

Moving in stages, from closed-for-all to open-for-some to fully-open, is reasonable. The aim, of course, is to be open-for-all, an achievable aim if a large enough proportion of the population is vaccinated. As we move to normality we should also make it possible for the non-vaccinated to access as many services as possible on reasonable grounds, for example, through the use of testing and masks.

It bears repeating that the best way to avoid these difficult decisions is for as many people as possible to be vaccinated, thus making social life safe for the unvaccinated as well as the vaccinated. For these reasons I have supported free vaccinations, stretching doses to vaccinate more people quickly through policies such as delaying the second dose and testing fractional doses, using single-shot vaccines, and developing nasal and oral vaccines.


Alex Tabarrok
Department of Economics
George Mason University

My Congressional Testimony

I thought the meeting went well. I made four points.

  • It is not too late to do more.
  • We should invest in nasal and oral vaccines.
  • We should vaccinate the world.
  • We should stretch doses through fractional dosing and delaying the second dose, this will be important to vaccinate the world quickly.

One observation. Lots of people are talking about vaccine hesitancy but I am one of the few people who have been talking about nasal and oral vaccines which are the only really solid approach to the issue that I have seen.

My best line:

The unvaccinated are the biggest risk for generating mutations and new variants. You have heard of the South Africa and Brazilian variants, well the best way to protect your constituents from these and other variants is to vaccinate South Africans and Brazilians.

I also got in the last word in Q&A when discussing the pause of J&J:

For the rest of the world it is important to underline that it is most important to get vaccinated now. Use the AstraZeneca vaccine, use the Johnnson & Johnson vaccine…don’t wait for Moderna or Pfizer, it is going to take too long…start your vaccination program early…vaccinate as quickly as possible, that is the route to health and wealth.

See Western Warnings Tarnish Vaccines the World Badly Needs for the beginnings of a disaster. Note that if J&J and AZ are tarnished or knocked out of the vaccine arsenal then dose stretching and investing in more capacity are going to be even more important.

I also submitted five excellent and important pieces to Congress:

Canadian statement on delaying the second dose.

National Advisory Committee on Immunization (NACI) Canada. 2021. “COVID-19 Vaccine Extended Dose Interval for Canadians: NACI Recommendation.” Government of Canada. March 3, 2021.

Value of vaccine capacity and additional investments.

Castillo, Juan Camilo, Amrita Ahuja, Susan Athey, Arthur Baker, Eric Budish, Tasneem Chipty, Rachel Glennerster, et al. 2021. “Market Design to Accelerate COVID-19 Vaccine Supply.” Science, February.

Efficacy of the first dose from NEJM.

Skowronski, Danuta, and Gaston Serres De. 2021. “Letter to the Editor on Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine.” New England Journal of Medicine, February 17, 2021.

Overview of dose stretching policies (with links in the online version).

Tabarrok, Alex. 2021. “What Are We Waiting For?” Washington Post, February 12, 2021, sec. Outlook.

A plan to vaccinate the world.

Agarwal, Ruchir, and Tristan Reed. 2021. “How to End the COVID-19 Pandemic by March 2022” SSRN. 2021.

The whole thing is here. My written testimony is here.

Trypanophobia or How to Alleviate Vaccine Hesitancy

A significant share of vaccine hesitancy is driven by fear of needles, trypanophobia. Adults don’t like to admit a fear of needles and less so that they would avoid a vaccine for fear of a needle. But trypanophobia is common and does reduce flu immunizations:

Avoidance of influenza vaccination because of needle fear occurred in 16% of adult patients, 27% of hospital employees, 18% of workers at long‐term care facilities, and 8% of healthcare workers at hospitals. Needle fear was common when undergoing venipuncture, blood donation, and in those with chronic conditions requiring injection.

Aside from fear of the needle, I think there is also a perception that needles are “serious medicine” and thus anything that comes in needle form must be serious or dangerous. In fact, vaccines are safer than many commonly used drugs that are taken orally.

Needle hesitancy is bad for the hesitant who don’t get protection from COVID and bad for everyone else who are further subject to transmission from unvaccinated carriers.

The best way to alleviate needle hesitancy is to get rid of the needle. Operation Warp Speed made smart investments in a fairly widely range of vaccines (we advised going wider) including a pill vaccine from VaxArt. The VaxArt vaccine has completed a Phase I trial with modest results and is moving into Phase II. Nasal vaccines are in development. The RadVac open science vaccine, for example, is a nasal vaccine available to anyone with a scientific bent willing to give an unapproved vaccine a try. CodaGenix has a nasal vaccine in Phase I trials as does Altimmune.

Aside from ease of delivery, a COVID nasal or oral vaccine may also be better than intramuscular injection because it stimulates the immune system at the first point of viral attack, the mucosal tissues in the nose, mouth, lungs and digestive tract. In addition, the mucosal immune system has some unique elements so you get a potentially stronger immune response more capable of neutralizing the virus quickly.

Operation Warp Speed investments generated trillions in value for billions in cost, a few additional smart investments in accelerating nasal and oral vaccines could pay off highly in mopping up vaccine hesitancy and moving us more quickly to herd immunity. We could even do a human challenge trial with nasal vaccine v. intramusucalar injection. Oral and nasal vaccines will also be great for kids and for booster shots.

Even at this late stage we are spending trillions on stimulus/relief and not enough on investment, especially on highly successful investment in vaccines.

Addendum: I know it probably won’t help but fyi, it’s a painless shot. Nothing to fear! Get a superpower and a donut afterwards. It will be memorable.

The Omission-Commission Error is Deadly

Britain will start a human challenge trial in January.

The Sun: Imperial College said its joint human challenge study involves volunteers aged 18 to 30, with the project starting in January – and results expected in May.

Initially, 90 volunteers will be given a dose of an experimental nasal vaccine.

They’ll then be deliberately infected with Covid-19.

But this is really just the first part of an excessively cautious study designed to “discover the smallest amount of virus it takes to cause a person to develop Covid-19 infection.” Moreover:

… it’s taken a few months to come to fruition, as before any research could begin the study had to be approved by ethics committees and regulators.

The omission-commission error is deadly. Notice that giving less than one hundred volunteers the virus (commission) is ethically fraught and takes months of debate before one can get approval. But running a large randomized controlled trial in which tens of thousands of people are exposed to the virus is A-ok even though more people may be infected in the latter case than the former and even though faster clinical trials could save many lives. Ethical madness.

Monday assorted links

1. Data on the oldest companies in the world.  Often small, and related to food and/or hospitality.  Often Japanese.

2. “The Trans-Universal Zombie Church of the Blissful Ringing is a religion that emerged in the context of a period of political uprising in Slovenia in 2012–13 and later consolidated into a church that now claims 12,000 members.

3. “We find that COVID-19 has likely become the leading cause of death (surpassing unintentional overdoses) among young adults aged 25-44 in some areas of the United States during substantial COVID-19 outbreaks.

4. While America has been dithering, good (but not surprising) news on AstraZeneca.  The vaccine may come to UK hospitals by November.

5. a16z podcast on textiles, with Virginia Postrel and Sonal Chokshi.

6. 12-minute nasal swab test coming to the UK.

7. Data on the French second wave.

Wednesday assorted links

1. Russian billionaire wants to buy cancelled Confederate statues.

2. “Nursing homes have new COVID-19 tests that are fast and cheap. So why won’t N.J. allow them to be used?

3. Where are the missing right-wing firms?  And Arnold.

4. The vaccine protocols.

5. The world forager elite.

6. An evidence-based return to work plan.

7. The nasal spray, which will be entering clinical trials.

8. On the Abraham Accords.

Shoring Up the Vaccine Supply Chain

Supply chains were hit hard early in the pandemic. Disinfectant couldn’t be produced because of a lack of bottles, tests couldn’t be processed because nasal swabs or PPE wasn’t available, the decline of passenger air traffic hit commercial delivery and so forth. I worry about forthcoming stresses on the vaccine supply chain. Billions of doses of vaccine will be demanded in the next year and a lot will depend on complicated supply lines including cold storage, air traffic, styrofoam, vials, bags, needles and many other inputs. Companies and the awesome team at CEPI (give them all a Nobel prize) are planning for vials and needles and other inputs but there are many non-obvious inputs higher up in the supply chain that also need shoring up.

Shark livers–they make vaccines better! From

Writing in Bloomberg, Scott Duke Kominers and I look at some of the odder inputs to vaccines like horseshoe crab blood, shark livers and the vaccinia capping enyzme, VCE. We are actually not too worried about horseshoe crab blood and shark livers as these are used in other industries. Shark livers, for example, are used to produce a lot of cosmetics so we should be able to divert supply as needed. VCE, however, is rarer.

DNA and mRNA vaccine technologies have shown promising results, and two of the leading vaccine contenders, from Pfizer Inc. and Moderna Inc., use mRNA technology. But mRNA has never been used to produce a commercial vaccine for humans, let alone at scale. And scaling these technologies may not be easy. In particular, mRNA degrades rapidly. To prevent this, it must be “capped” by a very rare substance called vaccinia capping enzyme.

Just over 10 pounds of this VCE is enough to produce a hundred million doses of an mRNA vaccine — but the current manufacturing processes for VCE require so much bioreactor capacity that making 10 pounds would cost about $1.4 billion. More important, global bioreactor capacity cannot support production at that level while also producing other vaccines and cancer-fighting drugs.

If we work hard now, we may be able to find more efficient means of producing VCE. Expanding bioreactor production and repurposing bioreactors from existing large-scale industrial applications will also help to lessen the pressure on the supply chains for multiple types of vaccines.

In addition to supply chains per se we also face the problem that companies are not raising prices enough. Ironically, this means that we need more public investment.

Of course, we might think that private companies would have incentives to coordinate supply chains themselves — and to some extent, they are doing so. But many have pledged to keep their vaccine prices close to costs, both out of altruism and because they may fear public backlash (or legal action) if they’re perceived as “price gouging” in the middle of a pandemic. And if companies don’t stand to profit much from Covid-19 vaccines, then they don’t have much incentive to invest in increasing capacity. In short: If prices can’t rise, then the only way to encourage companies to invest more in production is to reduce their costs — and that means we need public investment.

More generally, it’s not too late to be building more vaccine capacity and to repurpose bioreactor capacity from non-GMP sources, perhaps including veterinary and food sources. There are lots of vaccines in development. The science is promising. We need to take action now so that we can deliver on that promise.

Read the whole thing.

Save Grandma, Save the Economy

The meat supply is starting to fail. Meat processing factories seem especially susceptible to COVID-19 probably because of mist, chilled air circulation, the creation of aerosols and close worker contact. What other industries could be affected? What would happen if the energy, transportation, or pharmaceutical sector failed? We aren’t even sure which industries are critical. Who would have thought that nasal swabs would be a critical industry? In researching vaccine production I was stunned to learn that glass vials may be a bottleneck. Glass vials! How then do we best protect the workers in our critical industries? Should everyone else practice social distancing, closing of non-essential firms and work from home or should everyone else return to work as if everything were normal?

Social distancing, closing non-essential firms and working from home protect the vulnerable but these same practices protect workers in critical industries. Thus, the debate between protecting the vulnerable and protecting the economy is moot. “Lockdowns” protect vulnerable people and protect vulnerable industries. Save grandma, save the economy.

The point is simple but made formally in Social Distancing and Supply Disruptions in a Pandemic by Bodenstein, Corsetti and Guerrieri.

Abstract: Drastic public health measures such as social distancing or lockdowns can reduce the loss of human life by keeping the number of infected individuals from exceeding the capacity of the health care system but are often criticized because of the social and economic costs they entail. We question this view by combining an epidemiological model, calibrated to capture the spread of the COVID-19 virus, with a multisector model, designed to capture key characteristics of the U.S. Input Output Tables. Our two-sector model features a core sector that produces intermediate inputs not easily replaced by inputs from the other sector, subject to minimum-scale requirements. We show that, by affecting workers in this core sector, the high peak of an infection not mitigated by social distancing may cause very large upfront economic costs in terms of output, consumption and investment. Social distancing measures can reduce these costs, especially if skewed towards non-core industries and occupations with tasks that can be performed from home, helping to smooth the surge in infections among workers in the core sector.

Addendum: I wrote “lockdowns” because I am in favor of getting back to work with mass testing and safety protocols so I don’t think that a “lockdown” is necessarily the optimal policy. Indeed, I think we could get the meat processors back up and running with testing at the door and safety protocols. But we are not having a rational discussion about the tools and the investments that we need to reopen the economy. Instead, the people protesting to reopen the economy are also protesting against the use of a key tool to reopen the economy, masks! Welcome to crazy town.

Are humans constantly but subconsciously smelling themselves?

Here is the opening of a lengthy abstract of a new paper by Ofer Perl,, and it may help explain why it is so hard to avoid touching your face:

All primates, including humans, engage in self-face-touching at very high frequency. The functional purpose or antecedents of this behaviour remain unclear. In this hybrid review, we put forth the hypothesis that self-face-touching subserves self-smelling. We first review data implying that humans touch their faces at very high frequency. We then detail evidence from the one study that implicated an olfactory origin for this behaviour: This evidence consists of significantly increased nasal inhalation concurrent with self-face-touching, and predictable increases or decreases in self-face-touching as a function of subliminal odourant tainting. Although we speculate that self-smelling through self-face-touching is largely an unconscious act, we note that in addition, humans also consciously smell themselves at high frequency.

File under Questions that are Rarely Asked, via Michelle Dawson.

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