And Then There Were 33…The Latest 11 Covid Vaccines to Reach the Phase 3 Results Milestone

There’s been a big leap in the number of Covid vaccines known to have phase 3 results since my last catch-up post on this in January—from 22 vaccines then to 33 now. Some key points about the whole group, and highlights about the newcomers:

• The most common vaccine type in the group of 33 is the protein subunit vaccine, at nearly half of the group (45%, with 15 vaxes).
• China is the country that developed the most vaccines by far in this group, with a total of 7 vaxes. In all, 14 of the 33 vaccines were developed or co-developed in Asia.
• Some vaccines are now being evaluated primarily on signs of immune response, and several are being compared to other vaccines rather than placebo.
• For 3 of the vaccines added this time around, the phase 3 trial results are for use as a booster only, not primary vaccination. All are protein subunit vaccines, including one from the major pharmaceutical company, Sanofi.
• The first 2 self-amplifying mRNA Covid vaccines met their efficacy targets in phase 3 trials. They were both developed by US companies: Arcturus (manufactured and trialed in Vietnam) and HDT Bio (manufactured and trialed in India). Of at least 9 groups known to be testing mRNA Covid vaxes in 2020, 5 now have phase 3 results. One of them, CureVac’s, didn’t meet its minimum efficacy target.
• Vietnam’s homegrown vaccine, Nanocovax, has come in with one of the lowest costs and best adverse event profiles of all Covid vaccines. Efficacy was similar to many others in the Delta wave: very high against severe Covid disease, though considerably lower against symptomatic Covid. The cost, around $5 per dose, is lower than the AZ vax produced in India ($6).

Here are some links to help you navigate through the rest of this post:

• Overview of 33 vaccines
• Latest 11 vaccines with phase 3 results
• Addendum: List of all 33 vaccines
• Key terms used in this post (like confidence intervals and vaccine efficacy)

For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.

Overview of 33 vaccines

Close to half of these vaccines are protein subunit vaccines: 15 in all (45%). That’s almost as many as the inactivated, viral vector, and mRNA vaccines put together.

Vaccines by type

In this post, I’ve listed vaccines by the country they were developed in, not the manufacturers’ countries. The country that’s developed the most of these Covid vaccines is China, with 7. Altogether, 14 of the 33 vaxes were developed or co-developed in Asia (42%)—the same as Europe and North America combined.

Vaccines by region of development

Here are the vaccine numbers by the country of development:

• 8 vaccines: China
• 6 vaccines: USA
• 3 vaccines: Cuba
• 2 vaccines each: France, Germany, India, Russia
• 1 vaccine each: Australia, Canada, Iran, Japan, Kazakhstan, Netherlands, Taiwan, UK, Vietnam

Because vaccines are assigned to their developers above, it might be worth checking out the table below if you’re interested in this—they might not be the vaccines you’re thinking of. For example, this means that the “Pfizer vaccine” is assigned to Germany, because it was developed by BioNTech, the “J&J vaccine” is the Netherlands, because it was developed by Janssen, and so on.

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Latest 11 vaccines with phase 3 results

• Arcturus: one of the first 2 self-amplifying mRNA vaccines, developed in the USA, and produced by Vinbiocare in Vietnam
• Gemcovac: the second self-amplifying mRNA vaccine, stable at refrigerator temperatures, developed in the USA by HDT Bio and produced in India by Gennova
• Livzon: the first protein subunit Covid vaccine from China, booster results only
• Medigen: protein subunit vaccine from Taiwan, that now has an intranasal version in clinical trial
• Nanocovax: protein subunit vaccine from Vietnam
• QazVac: inactivated vaccine from Kazakhstan
• Razi Cov Pars: protein subunit vaccine with 3 doses, including a final intranasal dose (the first intranasal Covid vax rolled out globally)
• Sanofi: protein subunit vaccine with GSK adjuvant, from France, booster results only
• Shionogi: protein subunit vaccine, the first Covid vaccine from Japan, booster results only
• SK Bioscience: protein subunit vaccine, co-developed in South Korea and USA, produced by SK Bioscience
• Spikogen: protein subunit vaccine, developed in Australia and produced in Iran

Arcturus

Arcturus is a company from the US that developed 3 versions of its self-amplifying mRNA Covid vaccine, called ARCT-021, ARCT-154, and ARCT-165. All 3 went into an early stage clinical trial in the US and Singapore. Arcturus is a company from the US that developed 3 versions of its self-amplifying mRNA Covid vaccine, called ARCT-021, ARCT-154, and ARCT-165. All 3 went into an early stage clinical trial in the US and Singapore. ARCT-021 is being further developed with Duke-NUS university in Singapore, and another phase 1/2 trial was run for ARCT-021 there (results here). There’s another phase 2 trial for that version there as well.

Arcturus also licensed ARCT-154 to Vinbiocare, a pharmaceutical company in Vietnam. They went into a large phase 1/2/3 trial for over 19,000 people, 16,000 of them in phase 3. In April, Arcturus issued a press release announcing some phase 3 results. The Covid outbreaks during this trial were Delta and Omicron, and vaccine efficacy was:

• 55.0% (CI 47-62) against Covid-19 (not clear if that includes asymptomatic infection), and
• 95.3% (CI 80-99) against severe and fatal Covid-19 (2 cases in the vaccine group versus 41 for placebo).

There’s too little detail about adverse events in the press release to comment on, and I haven’t seen any publications of earlier trial results. (As far as I know, there haven’t been preclinical results either.)

Arcturus is also planning a trial for ARCT-154 as a booster vaccine.

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Gemcovac

This is a self-amplifying mRNA vaccine, and it is stable at refrigerator temperature. It was developed by HDT Bio in the USA, and is manufactured in India by Gennova. Only preclinical results have been published for this vaccine, as far as I know, although data from phases 1, 2, and 3 are included in the drug’s Summary of Product Characteristics.

A phase 2/3 trial was run in India. It included 2,992 people randomized to Gemcovac, and 998 to Covishield (the Indian version of the AstraZeneca vaccine). Most of the participants were men (78%). The vaccine was shown to be non-inferior (similar) to the AZ vaccine based on signs of immune response.

One of the advantages claimed for self-amplifying mRNA vaccines is that they can be used in lower doses, and so have fewer adverse events. The Gemcovac vaccine has a much lower rate of adverse events than the Moderna and Pfizer vaccines. The most common systemic adverse event reported was fever, at 16%. For the first 2 mRNA vaccines it was much higher: for Moderna, the most common was fatigue at 65%, and for Pfizer, fatigue at 56%.

See all records for this vaccine.

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Livzon

This protein subunit vaccine, called V-01, was developed in a collaboration between the Chinese Academy of Sciences and Livzon Mabpharm. It’s in a 22,000-participant phase 3 trial in Indonesia, the Philippines, and Russia that started in August last year. There aren’t results from that yet, though there are preclinical results and results from the early phase trials.

The first phase 3 results for this vaccine come from a booster trial, with 10,218 participants in Malaysia and Pakistan during the Omicron wave. Over 70% of the participants were men, with 5% aged 60 or older. The participants had been vaccinated with 2 doses of inactivated vaccine 3-6 months earlier, either CoronaVac (73%) or the Sinopharm Beijing vaccine. They were randomized to either a dose of V-01 or placebo. Vaccine efficacy was 47.8% (CI 23–65) against symptomatic Covid-19, with a large increase in neutralizing antibodies. There were 38 cases of symptomatic Covid in the boosted group versus 72 in the placebo group. They got sequencing results for 69, and 91% were Omicron. Vaccine efficacy was:

• 47.8% (CI 23-65) against symptomatic Covid-19 for the whole group;
• 47.0% (CI 11-69) against symptomatic Covid-19 caused by Omicron; and
• 79.9% (CI −72–98) against symptomatic Covid-19 caused by Delta.

The authors reported that there weren’t enough people with severe Covid to calculate efficacy rates. The rate of adverse events was similar between the V-01 boost and placebo.

See all records for this vaccine.

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Medigen

This protein subunit vaccine with a Dynavax adjuvant is called MVC-COV1901, and it’s from Medigen in Taiwan. The vaccine had a very large phase 2 trial (3,844 participants), and phase 2 results for adolescents have also been reported. The phase 3 trial was a non-inferiority trial in Paraguay, comparing signs of immune response between the Medigen vaccine and the AstraZeneca one. It included 1,030 participants. The authors concluded the Medigen vaccine had similar rates of seroconversion to the AZ vax, with superior neutralizing antibody response.

There are trials underway for a version of this vaccine adapted to the Beta variant, and an intranasal version.

See all records for this vaccine.

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Nanocovax

This protein subunit vaccine was developed by Nanogen Pharmaceutical Biotechnology, a pharmaceutical company in Vietnam. Preclinical results were published in 2021, and results from phase 1/2 in March 2022. Results of the phase 3 trial were released soon after. The phase 3 trial was running in Vietnam during the Delta wave. Vaccine efficacy was:

• 51.5% (CI 34-64) against symptomatic Covid,
• 93.3% (CI 62-98) against severe Covid or death.

The rate of adverse events was very low, similar to placebo after the first dose, and only a few percentage points higher than placebo on a few outcomes after the second dose (fatigue and aches in the muscles and joints).

Nanocovax is one of the lowest cost Covid vaccines, at around $5 a dose. For context, the African Union was offered Moderna for $32 or more a dose, Pfizer $13.50, Sputnik V $19.50, J&J $10 (single dose vax), and AZ and Novavax produced by the Serum Institute of India at $6 a dose.

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QazVac

QazVac is an inactivated vaccine produced by Kazakhstan’s public research agency, the Research Institute for Biological Safety Problems. There haven’t been any preclinical results as far as I know, but phase 1/2 trial results were published last year.

The 3,000-participant phase 3 trial was run in Kazakhstan, with 4 people randomized to vax for every 1 person randomized to placebo. Over 90% of the participants were Asian. The trial was pre-Omicron, and original, Alpha, and Delta variants were circulating. Vaccine efficacy was:

•  82·0% (CI 71–89) against symptomatic Covid-19,
• 1 vaxed person developed severe Covid, no one did in the placebo group.

The rate of adverse events was very low, and all were reported as mild.

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Razi Cov Pars

This is a 3-dose protein subunit vaccine, with 2 injections followed by an intranasal dose. It is the first intranasal vaccine that’s been rolled out. The vaccine was developed by the Razi Vaccine and Serum Research Institute, a public institute under the Ministry of Agriculture.

The only full publication of results is for preclinical studies in 4 species. The phase 3 trial is for over 41,000 people, running in Iran. The vaccine is being compared to 2 injections of the Sinopharm Beijing vaccine. Some results for the first 24,000 participants have been released to the press. The rate of Covid was reportedly more than twice as high for the Sinopharm vax as for Razi Cov Pars, with no hospitalizations for Covid in the Razi Cov Pars group versus 5 in the Sinopharm vax group.

The vaccine is also in a clinical trial for adolescents (from age 12).

See all records on this vaccine.

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Sanofi

This is a protein subunit vaccine, called CoV2 preS dTM. It was developed by Sanofi, and includes an adjuvant produced by GSK. There are preclinical and early phase trial results for the vaccine. The phase 3 trial results are for using this vaccine as a booster after Moderna or Pfizer vaccination.

Sanofi is running a phase 2/3 trial studying immune responses to the original version of their vaccine, and a version adapted for the Beta variant, as well as a bivalent version including both. That trial also includes groups testing the Sanofi vax as a booster for people who were previously mRNA vaccinated. So far, there has just been a short description of some results from that trial in a press release: the Beta-adapted vaccine generated much higher immune responses to variants of concern, including doubling the neutralizing antibody response to Omicron.

Results of a second booster trial of have been released. In this one, people who had previously been vaccinated with the Pfizer vaccine were randomized to a booster of the original Sanofi vax, the Beta-adapted version, or a third dose of Pfizer vax. The Beta-adapted version of the Sanofi vax induced greater immune response than the original versions of either the Pfizer or Sanofi vaxes.

See all records for this vaccine.

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Shionogi

This is the first Covid vaccine from Japan that has reached this stage, developed by the Shionogi pharmaceutical company. It’s a protein subunit vaccine called S-268019-b, with preclinical and phase 1/2 trial results released. Several phase 3 trials are underway: a phase 2/3 trial for 3,100 people (no control group); a phase 3 trial using the Shionogi or Pfizer vaccine as a booster in 300 people previously Pfizer-vaxed; a phase 3 trial comparing 2 doses of Shionogi vaccine with 1 dose after the AZ vaccine, in 1,000; and a 54,915-participant phase 3 placebo crossover trial running in Vietnam. (I wrote about crossover trials for Covid vaccines here last year.)

Results have been released for 204 people in the first of those trials—using the Shionogi or Pfizer vax 6 or more months after primary vaccination with the Pfizer vaccine. The authors report that the vaccine met their immune response target for non-inferiority (similarity to the Pfizer vax). The rate of adverse events was somewhat lower for the Shionogi booster than the Pfizer one.

See all records for this vaccine.

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SK Bioscience

This is a protein subunit vaccine called GBP510, co-developed by SK Bioscience in South Korea, and the University of Washington, USA. Preclinical and phase 1/2 trial reports have been published. The phase 3 trial ran in New Zealand, the Philippines, South Korea, Thailand, Ukraine, and Vietnam. Results reported in a press release that in 4,037 participants, immune responses to the vaccine were non-inferior (similar) to the AZ vaccine.

See all records on this vaccine.

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Spikogen

Spikogen is a protein subunit vaccine developed by Vaxine, an Australian pharmaceutical company, and including their adjuvant, AdVax. Spikogen is manufactured by CinnaGen, an Iranian pharmaceutical company. Preclinical and phase 2 trial results have been published. Early phase trials were run in Australia, and later trials in Iran.

I can’t read Farsi, so I’m not sure if more detail is available on the phase 3 trials than I have found: I don’t believe the full results have been released. The primary vaccination trial was for 16,786 participants, with a placebo group, and there was a 300-participant booster trial, using Spikogen after a previous course of inactivated Covid vaccine. There’s a report of a press conference presenting some narrative results, without including data. The trial was run during Iran’s Delta wave. There’s a website for the vaccine, which says that the efficacy of the vaccine was 60.65%.

There is also a trial of Spikogen underway in children from the age of 5, and adolescents.

See all records for this vaccine.

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Addendum: All vaccines with phase 3 results

* Latest group of vaccines

Vaccine “Name”	Developer	Country	Vaccine Type
Abdala	Centre for Genetic Engineering and Biotechnology	Cuba	Protein subunit
Arcturus (ARCT-154)*	Arcturus	USA	Self-amplifying mRNA
AstraZeneca	Oxford University	UK	Viral vector (adenovirus)
CanSino	CanSino Biologics	China	Viral vector (adenovirus)
Clover	Clover Biopharmaceuticals	China	Protein subunit
Corbevax	Baylor College of Medicine (Biological E version from India)	USA	Protein subunit
CoronaVac	Sinovac	China	Inactivated
Covaxin	Bharat Biotech	India	Inactivated
CureVac	CureVac	Germany	mRNA
Gemcovac*	HDT Bio	USA	self-amplifying mRNA
SK Bioscience*	SK Bioscience and the University of Washington	South Korea/USA	Protein subunit
J&J	Janssen	Netherlands	Viral vector (adenovirus)
Livzon* (booster)	Livzon Pharmaceuticals	China	Protein subunit
Medicago	Medicago	Canada	Virus-like particles
Medigen	Medigen Vaccine Biologics	Taiwan	Protein subunit
Moderna	Moderna	USA	mRNA
Nanocovax*	Nanogen Pharmaceutical Biotech	Vietnam	Protein subunit
Novavax	Novavax	USA	Protein subunit
Pfizer	BioNTech	Germany	mRNA
QazVac	Research Institute for Biological Safety Problems	Kazakhstan	Inactivated
Razi Cov Pars*	Razi Vaccine and Serum Research Institute	Iran	Protein subunit
Sanofi*	Sanofi	France	Protein subunit
Shionogi*	Shionogi	Japan	Protein subunit
Sinopharm Beijing	Sinopharm BBIBP	China	Inactivated
Sinopharm Wuhan	Sinopharm WIBP	China	Inactivated
Soberana 2	Finlay Institute	Cuba	Protein subunit
Soberana Plus	Finlay Institute	Cuba	Protein subunit
Spikogen*	Vaxine	Australia	Protein subunit
Sputnik Light (V’s Shot 1)	Gamaleya Institute	Russia	Viral vector (adenovirus)
Sputnik V (Shot 2)	Gamaleya Institute	Russia	Viral vector (adenovirus)
Valneva	Valneva	France	Inactivated
Zifivax (ZF2001)	Anhui Zhifei Longcom	China	Protein subunit
ZyCov-D	Zydus Cadila	India	DNA

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For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.

Updated shortly after posting: Alexey Merz pointed out that I hadn’t originally included GBP510. I had overlooked a press release. On August 6, I added Valneva’s inactivated vaccine: I had overlooked a press release in October 2021, and thanks to Pog for pointing out the omission. And the EMA published their assessment report on the Valneva vaccine in June 2022. Rohan Gurjar pointed out that I had missed HDT Bio’s vaccine, which had been authorized in India in June, without public release of phase 3 data: it’s included in the drug’s prescriber information, Summary of Product Characteristics.

All my Absolutely Maybe Covid-19 vaccine posts

All previous Covid-19 posts at Absolutely Maybe

My posts at The Atlantic, at WIRED, and debunking posts at my personal website.

Disclosures: My interest in Covid-19 vaccine trials is as a person worried about the virus, as my son is immunocompromised: I have no financial or professional interest in the vaccines. I have worked for an institute of the NIH in the past, but not the one working on vaccines (NIAID). More about me.

The cartoons are my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.)

Data tables for charts

Vaccines by type:

Protein subunit	15
Inactivated	6
Viral vector	5
mRNA*	5
DNA	1
Virus-like particles	1
Total	33

Vaccines by region of developer:

Asia	13
North America	7
Europe	6
Caribbean	3
Eurasia	2
Middle East	2
Australasia	1
Total	34

Key terms used in this post

• Homologous vaccine schedules have the same vaccine for each dose. When the doses aren’t all of the same vaccine, that’s called heterologous – what I’m calling “mixed” in this post. The first shot in a multi-dose vaccine schedule is called the prime: doses thereafter are boosts.
• Vaccine efficacy is a rate of risk reduction in symptomatic Covid-19 unless otherwise specified. Vaccine efficacy of 80% or 90% means if a vaccinated person is exposed to the virus, their risk of getting the disease is lowered by that proportion, so it depends on how high their risk of being exposed, and that varies. It’s not an absolute drop in percentage points. (Efficacy is for results on disease outcomes from phase 3 clinical trials; effectiveness studies follow that.)
• When available, a range of statistical certainty for efficacy is shown, eg 92% (CI: 88-95). The distance between 88% and 95% in this example is small: it means there is a lot of certainty that 92% is about what we can expect. However, the wider that range is, the more uncertain we are.
• The rate of efficacy set for whether a Covid vaccine works well enough is 50% (with a CI starting at 30% at least).
• And I have a post explaining the terms used, and assessment processes, for adverse events and safety in these trials – including the difference between “severe” and “serious”.