Adapting for Variants: Early Results or Trials Underway for 38 Versions of 17 Covid Vaccines

Seventeen vaccines with at least one variant-adapted version sounds like a lot. But none are actually in use yet. And given all the hype about how quickly and easily adapted vaccines could be delivered, it’s remarkable how little data we’ve seen well over a year since the first variant of concern emerged. We had gotten used to a high level of transparency about the development of the Covid vaccines leading the pack in the US and Europe. That’s not the rule any more.

For example, I haven’t been able to find any preclinical reports for the various BNT/Pfizer adapted versions in clinical trials, including for the Alpha variant. Another example: even when there are late stage clinical trials, protocols aren’t to be found, either.

Before we get to the studies and results we can see, let’s zoom out to the big picture. Several vaccination strategies are being studied for expanding or strengthening our immune systems against Covid variants:

• Boosting with an additional dose of the same vaccine;
• Boosting with a dose of a different vaccine (heterologous vaccination);
• Adapting a vaccine for a variant;
• Multivalent vaccines – combinations of original plus adapted version(s), or combinations of adapted versions;
• Vaccine so wide-ranging, it’s hoped to be more or less variant-proof – or even effective for all coronaviruses.

I posted a roundup of evidence and ongoing trials for the first 2 of those strategies in late January. In general, they both increase protection against variants, with heterologous boosting often making a particularly large difference for vaccines with somewhat lower initial effectiveness. (That post included a table listing laboratory studies of responses to Delta and/or Omicron after boosters: an updated version of that is below this post.)

This post is looking at the next 2 strategies: adapted and multivalent vaccines.

My key takeaways? We seem to be on the brink of seeing meaningful clinical trial results for some adapted vaccines. And from the research results that have been released so far, it seems likely that at least some of these vaccines will provide better protection against the variants circulating now – and, critically, perhaps broaden immunity enough for greater protection from the next ones.

Just as the original vaccines based on the virus’ early strains reduced the risk of severe outcomes from variants that were very different, adapted vaccines based on variants that are no longer a threat could do that, too. For example, as we’ll see later in this post, a “press teaser” finding from a randomized trial suggests the Alpha-adapted BNT/Pfizer vaccine could possibly be substantially more protective against Omicron than the original formulation. (Proviso here: the companies released far too little information about this to be sure about how good it was.) And Sanofi’s Beta-adapted protein subunit vaccine may even have increased the potential for protection against original SARS in a preclinical study. On the other hand, some don’t work as well as another shot of the original.

This next stage of vaccine development is very complex, as researchers grapple with a shape-shifting virus, and the complexity of so many possible vaccine adaptations, too. Multivalent vaccine development escalates that complexity: that’s a mixture of vaccines in one dose, which adds questions to the list about multiple possible vaccine combinations and how much of each to add to the mix.

All this comes as an overlay to the complicated issues of boosting with different vaccines if/when we have adapted vaccines tested only in people who had that same vaccine. Today, 63% of the world’s people have had at least a dose of a vaccine – and it’s a real patchwork of vaccines, often changed up along the way to 2 or 3 shots. And as if all that isn’t complex enough, there’s the question of intranasal administration: one of the vaccines in this post suggests that could make a meaningful difference for at least some adapted vaccine boosters.

There’s lots more to cover, though, so let’s dig in. Here’s how I’ve broken this post down:

• Overview of vaccines, variants, and studies
• Digging into the results
• Full list of studies on variant-adapted Covid vaccines and combinations
• Addendum: Updated list of laboratory studies including immune responses to Delta and/or Omicron after boosters

Overview of vaccines, variants, and studies

I found 39 studies reported or underway for 38 adapted vaccines or combinations, from 17 vaccine groups – 7 of which have original formulations of vaccines in use in at least one country. Most are mRNA or protein subunit vaccines. There are sure to be other adapted versions that don’t have published results or clinical trials registered, or for vaccines that are earlier in the pipeline, so expect a stream to keep coming. (I monitor vaccines when they release preclinical or clinical results, as well as any that have announced a phase 3 trial.)

The vaccines in this collection include adaptations for 4 of the 5 variants of concern – none are for Gamma. There are vaccines adapted to 1 or 2 of them, and one vaccine adapted to all 4. The variants of concern so far have points in common as well as differences with the original virus that vaccines were formulated to recognize. Here’s a diagram showing how much the 5 variants of concern vary genetically (by Stuart Ray of John Hopkins):

Another variant of concern could be close to what we’ve already encountered – or it could strike out in a newer direction, as Omicron did. The studies on the impact of adapted vaccines will help us learn what can strengthen immune systems to face SARS-CoV-2 variants. The studies tallied in this post include:

• Results of 19 preclinical studies.
• 20 clinical trials underway, mostly phase 2, for around 16,500 participants globally, plus unstated number for Sanofi vaccine (possibly 10,000).
• Results for subsets of clinical trial participants for adaptations of 1 vaccine (Moderna), and some fragments of data from another (BNT/Pfizer).

Most of the vaccines are ones that aren’t yet rolled out in their original formulation – and for one of them, the first formulation is already adapted for variants (Alpha and Beta, with a later version covering Alpha, Beta, Delta, and Omicron).

The 17 vaccines that have adapted versions include:

• 7 mRNA vaccines and 1 self-amplifying RNA, 5 protein subunit vaccines, 2 adenoviral vector vaccines, 1 inactivated vaccine, and 1 DNA vaccine. (One of the mRNA vaccines is lyophilized (freeze-dried) and one of the protein subunit vaccines has an intranasal version of adapted vaccine.)
• 7 that are already in use in original formulation (AstraZeneca, BNT/Pfizer, CovIran (Shifa Pharmed), J&J, Medigen, Moderna, Novavax) – 4 of those with adapted versions in clinical trials (AZ, BNT/Pfizer, Medigen, and Moderna).
• 12 that are multivalent, and another that’s called a hybrid – it’s not a mix of 2 vaxes, but it’s targeted to 2 variants. They’re nearly all bivalent – including 2 versions of the vaccine – but one is quadrivalent: for protection against 4 strains of the virus (Alpha, Beta, Delta, and Omicron).

Digging into the results

Overall, there is a lot of uncertainty around these findings. They are almost all very small, preclinical studies. Some carry more weight than others, though, because they’re better-designed and conducted, with better reporting of what was done.

Animal results aren’t going to be a precise substitute for what happens in people, but there’s a spectrum here, too. Data in non-human primates is likely to be closer to what could be expected in humans, for example. Confirmation of results in experiments in more than one type or species of animal strengthens confidence in the reliability of conclusions, as well. And there can be differences between the techniques used in the studies – such as whether researchers analyzed immune responses in enough ways, and used tests based on actual viruses, or pseudovirus tests only.

There are 2 broad types of preclinical studies here:

• Studies of potential immunity only – analyzing immune responses in the animals, to identify whether they might be able to provide protection against particular variants;
• Challenge experiments, where the researchers try to infect the animals with virus after vaccination, and then analyze immune responses as well as other outcomes like weight loss (which suggests severe disease), and infection and viral loads.

Although I looked at a range of aspects of the studies to consider how to weigh them, in my opinion, whether or not the researchers included challenge experiments and/or randomized non-human primates turned out to be markers for dividing this set of studies into a “stronger” and a “weaker” group.

I’ve also looked at what the researchers conclude about antibody/antigenic imprinting (“original antigenic sin”). That’s when the immune system is so firmly influenced by a first encounter to a vaccine or antigen, its responses are heavily shaped by that original memory. (Derek Lowe discusses this phenomenon here). If that happens with a Covid vaccine, then a variant-adapted booster mightn’t have much impact. But I don’t have the technical expertise to discuss the design choices of the various adaptations made to the vaccines, and their possible implications.

First up, I’ve got a table showing the variant-specific vaccines that have public results, tagging those that have challenge experiments. After that, I discuss some issues I think are noteworthy, followed by a brief overview of results, vaccine by vaccine. That’s broken down into a pair of tables – for those with stronger and weaker evidence – so that the ones I think have greater uncertainty are clearly separated.

There are links to get you to the studies in 2 places: the overviews include links to the records for the vaccines in my collection – split into the ones for adapted vaccines, and all records. That’s a lot to navigate for the vaccines with many studies, though. So there are links to each individual study, whether or not they have results, in the full list of studies.

Vaccines with results for adapted versions for variants

* Includes challenge experiment(s)

Variant	Preclinical (non-human animals)	Clinical (human)
Alpha	HDT Bio (saRNA)*	BNT/Pfizer
Beta	ACM Biolabs (protein subunit – intranasal)* AstraZeneca (AZ) (adenoviral) Clover (protein subunit) HDT Bio (saRNA)* J&J (adenoviral) Moderna (mRNA)* Novavax (protein subunit)* Sanofi (protein subunit)	Moderna
Delta	Academia Sinica Taiwan (mRNA) Shenzhen Rhegen (mRNA – lyophilized)*	BNT/Pfizer Moderna
Omicron	Academia Sinica Taiwan (mRNA) Chinese Academy of Military Sciences/Walvax (mRNA) Chinese Academy of Sciences (mRNA) CovIran (Shifa Pharmed) (inactivated) HDT Bio (saRNA) Moderna (mRNA)* Shanghai Key Laboratory Fudan (DNA) Shenzhen Rhegen (mRNA – lyophilized)*

There’s a lot of variety in these experiments – for example, whether or not they were testing the vaccine as a booster or a primary series (the first vaccination cycle, which is usually 2 shots). And there’s a lot of variety in the results, too. Most of the researchers conclude the vaccines could be an improvement on original formulations, but we won’t know if the differences are meaningful until we see how they work in people.

The question of “antigenic sin” has gotten a fair bit of attention in discussions on social media, as some researchers have suggested it might be a factor in the results of the vaccine they studied. However, most don’t. Some of the “weaker” group of studies either didn’t test the vaccine as a booster, or had no comparison group, so the question is very open for them.

There are only reports from studies in humans for 2 vaccines, BNT/Pfizer and Moderna.

For the first, BNT/Pfizer’s, it’s results from a randomized trial – but it was just a single slide in a press briefing, with nowhere near enough information to know how certain we can be about the results presented. It was for the ability to neutralize Omicron after vaccination with an Alpha-adapted variant, one for Delta, or a bivalent one of both. That they had this data suggests that BNT/Pfizer will be first past the post in the late stage clinical trial results race again.

The second, Moderna’s, has plenty of data, but it’s actually more complicated. While I think researchers for this vaccine had the strongest methodology of any of the preclinical studies (by Ying and colleagues, 2021), the clinical research reports are problematic. They are 2 exploratory studies, where they’ve taken small subsets of participants from more than a single study each time, without the selection process being fully described, and with other factors driving up the risk of bias.

For now, then, we’re really left with the preclinical studies. So finally, some points I think are noteworthy from those:

• When an adapted vaccine didn’t seem to do better than the original vaccine, that tended to be because of apparently weaker potential to protect against other versions of the virus it wasn’t targeted at – the adapted vaccines typically worked well against the variant they were aiming for.
• Multivalent vaccines didn’t always do better, but they mostly worked at least as well as the most protective vaccine in the mix, and sometimes better.
• The number of variants tested for ability to respond in these studies was often quite small: many were done before the recent variants had emerged, for example. Still, many of the vaccines seemed to have a very broad range of potential protection. I already mentioned an example of one that was widely tested: Sanofi’s protein subunit vaccine may even have increased protection for the original SARS, which is a different coronavirus. (It improved outcomes for all the SARS-CoV-2 variants tested, too – original, Alpha, Beta, Gamma, and Delta.)
• One of the mRNA vaccines was lyophilized (freeze-dried) – from Shenzhen Rhegen Biotech and other collaborators in China.
• As I mentioned early in this post, there was an intranasal version of an adapted vaccine in this set of studies, and that may have enhanced its potential effectiveness. It’s for the protein subunit vaccine from ACM Biolabs (a company based in Singapore and Switzerland). (There are quite a lot of studies on intranasal or other mucosal delivery of a variety of Covid vaccines, but I haven’t added a tag for that yet in my collection – though I’m sure that’s just around the corner!)

Overview of results for stronger studies*

* Includes challenge experiment and/or randomized non-human primates, and additional stronger preclinical research methods, such as live virus assays, multiple animal types, and/or randomization of other animals.

** Includes include clinical research.

Vaccine Variant(s)	Signs of improvement over original?	Records
**BNT/Pfizer (mRNA) Alpha, Alpha+Delta	Possibly yes (as a booster) (Only tested against Omicron)	Adapted All
HDT Bio (saRNA) Alpha, Beta, Omicron	Possibly yes (alone as a primary series) Possibly not as a booster* (*Only Omicron version tested as booster)	Adapted All
ACM Biolabs (protein subunit) Beta, Original+Beta	Possibly yes for intranasal version (alone as a primary series) Multivalent, possibly not* (*Not tested in an intranasal version)	Adapted All
J&J (adenoviral) Beta	Possibly yes (as a booster)	Adapted All
**Moderna (mRNA) Beta, Original+Beta, Delta, Beta+Delta, Omicron	Mixed results – roughly similar to original	Adapted All
Novavax (protein subunit) Beta, Original+Beta	Possibly yes (alone or as booster)	Adapted All
Sanofi (protein subunit) Beta	Possibly yes, adjuvanted or multivalent (as booster to the original vax or Sanofi’s mRNA vax)	Adapted All
Shenzhen Rhegen (mRNA, lyophilized) Delta, Omicron	Possibly yes for Delta adaptation (alone as a primary series) (Possibly not for Omicron adaptation – weaker evidence)	Adapted All

Overview of results of weaker studies

Vaccine Variant(s)	Signs of improvement over original?	Records
AstraZeneca (adenoviral) Beta, Original+Beta	Possibly not (as primary series or booster)	Adapted All
Clover (protein subunit) Beta, Original+Beta	Possibly yes (as primary series or booster)	Adapted All
Academia Sinica Taiwan (mRNA) Delta, Delta+Omicron, Hybrid with characteristics of Delta and Omicron	Possibly yes (as primary series for Delta and Delta+Omicron versions) Possibly not for Omicron or hybrid versions	Adapted All
Chinese Academy of Military Sciences/Walvax (mRNA) Omicron	No data for comparison to original	Adapted All
Chinese Academy of Sciences (mRNA) Omicron	Possibly not (as primary series – not tested as booster)	Adapted All
Shanghai Key Laboratory Fudan (DNA) Omicron	Possibly yes (as a booster)	Adapted All
Shifa Pharmed (inactivated) Omicron	No data for comparison to original	Adapted All

Full list of studies on variant-adapted Covid vaccines and combinations

Listed alphabetically by vaccine technical name; booster status detailed when previous vaccine is from a different developer

* Original vaccine rolled out in at least 1 country in February 2022

Vaccine, type, manufacturer	Variant(s) adaptation	Participants	Location(s)	Research phase
Ad.COV2-S Adenoviral J&J*	Beta	24 non-human primates (macaques).	USA.	Preclinical. Results.
ARCoV mRNA Chinese Academy of Military Sciences/Walvax	Omicron	At least 17 mice (2 types) (number unclear).	China.	Preclinical. Results.
B1V1-CovIran Inactivated Shifa Pharmed*	Omicron	45 mice, 2 guinea pigs.	Iran.	Preclinical. Results.
BNT162b mRNA BNT/Pfizer*	Alpha; Delta; multivalent (Alpha & Delta)	1,245 people.	South Africa, Turkey, USA.	Phase 2. (Subset report in a press briefing.)
	Beta	137 people.	Germany.	Phase 2.
	Omicron	1,420 people (according to press release).	Not specified – could be Brazil, Canada, South Africa, USA.	Substudy D in phase 3 trial.
ChAdOx1 Adenoviral vector AstraZeneca (AZ)*	Beta; multivalent (original + Beta)	Mice, number unclear (5-7 per group, ca 7 groups).	UK.	Preclinical. Results.
	Beta	2,848 people.	Brazil, Poland, South Africa, UK.	Phase 2/3.
CoV2 preS dTM Protein subunit Sanofi	Beta; multivalent (original + Beta)	40 non-human primates (macaques).	USA.	Preclinical. Results.
	Multivalent (original + Beta)	Not stated (whole trial is 722 people).	Australia, France, Honduras, Kenya, Spain, UK, USA.	Phase 2/3 trial.
	Multivalent (original + Beta)	Possibly 10,000 people.	Colombia, Ghana, Honduras, India, Japan, Kenya, Mexico, Nepal, Sri Lanka, USA.	Phase 3 trial.
HGCO19 saRNA HDT Bio	Alpha; Beta	20 mice and 24 hamsters.	USA.	Preclinical. Results.
	Omicron	15 mice and 18 hamsters.	USA.	Preclinical. Results.
mRNA-1273 mRNA Moderna*	Beta; multivalent (original + Beta)	30 mice (number unclear).	USA.	Preclinical. Results.
	Beta; multivalent (original + Beta)	Mice (2 types), number unclear (6-9 mice per group, 4 groups in 2 experiments).	USA.	Preclinical. Results.
	Beta	32 non-human primates (macaques).	USA.	Preclinical. Results.
	Beta	135 people.	USA.	Phase 1.
	Beta; multivalent (original + Beta)	660 people.	USA.	Phase 2. Results (for subset of 80, 60 from one study and 20 from another).
	Multivalent (original + Beta); Delta; multivalent (Beta + Delta)	3,620 people.	USA.	Phase 2/3 trial. Results (for 120 people, including a subset of 100 from 5 of the 8 trial arms, plus 20 unboosted people from the main phase 3 trial).
	Omicron	16 mice (3 types) (number unclear).	USA.	Preclinical. Results.
	Omicron	16 non-human primates (macaques).	USA.	Preclinical. Results.
	Omicron	2,924 people (aged 16 or older).	UK.	Phase 2/3 trial.
	Omicron (and multivalent – unspecified)	300 people.	USA.	Phase 2 trial. (Press release – extension of other registered trials, but not clear which.)
mRNA-RBD mRNA Chinese Academy of Sciences	Omicron	21 mice.	China.	Preclinical. Results.
MVC-COV1901 Protein subunit Medigen*	Beta	160 people.	Taiwan.	Phase 2 trial.
NVX-CoV2373 Protein subunit Novavax*	Beta, multivalent (original + Beta)	>80 mice; >9 non-human primates (baboons) (numbers unclear).	USA.	Preclinical. Results.
SCB-2019 Protein subunit Clover	Beta, multivalent (original + Beta)	Mice, number unclear (16-32 per group in first stage with 4 groups).	China.	Preclinical. Results.
	Beta	152 people.	Australia.	Phase 1 trial.
SCTV01 Protein subunit Shenzhou Cell Engineering (Sinocelltech)	Multivalent (Alpha + Beta)	752 people.	China.	Phase 1/2 trial. (Additional info source)
	Multivalent (Alpha + Beta)	300 people.	United Arab Emirates.	Phase 1/2 trial (as booster after 2 doses of mRNA vaccine).
	Multivalent (Alpha + Beta)	300 people.	United Arab Emirates.	Phase 1/2 trial (as booster after 2 doses of inactivated vaccine).
	Multivalent (Alpha + Beta)	240 people (aged 12 and over).	Not stated.	Phase 2 trial (single dose of multivalent vaccine or BNT/Pfizer after 2-dose Sinopharm Beijing vaccine)
	Multivalent (Alpha + Beta)	600 people.	Not stated.	Phase 2 trial (single dose of multivalent, BNT/Pfizer, or Sinopharm vaccine after previous 2-doses of Sinopharm, Moderna, or BNT-Pfizer vaccines or Covid infection)
	Multivalent (Alpha + Beta), multivalent (Alpha + Beta + Delta + Omicron)	300 people (aged 12 and over).	Not stated.	Phase 2 trial (one of each, or 2 of the 4-variant version, or single dose Sinopharm Beijing vaccine plus 4-variant version).
	Multivalent (Alpha + Beta + Delta + Omicron)	360 people.	Not stated.	Phase 2 trial (2 doses multivalent, or dose each of BNT/Pfizer and multivalent, or 2 doses BNT/Pfizer – after 2 doses of Moderna or BNT-Pfizer)
Unnamed mRNA Academia Sinica Taiwan	Delta, Omicron, hybrid (characteristics of Delta + Omicron), multivalent (Delta + Omicron)	Mice, number unclear.	Taiwan.	Preclinical. Results.
Unnamed Protein subunit (intranasal) ACM Biolabs	Beta, multivalent (original + Beta)	5 mice, 48 hamsters.	Singapore, USA.	Preclinical. Results.
Unnamed DNA Shanghai Key Laboratory Fudan	Omicron	22 mice.	China.	Preclinical. Results.
Unnamed mRNA (lyophilized) Shenzhen Rhegen Biotech + others	Delta, Omicron	36 mice (2 types).	China.	Preclinical. Results.

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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.

Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.

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.)

The representation of similarity between Covid variants of concern comes from Wikimedia Commons, based on data from NextStrain on December 1, 2021 by Stuart Ray from Johns Hopkins (wiki name, Soupvector).

Update [February 24, 2022]: Added Sanofi phase 3 trial to studies underway.

Updated list of laboratory studies including responses to Delta and/or Omicron after boosters

This is an update of a list included in a post from late January, including a summary of the studies up to January 25.

Vaccine(s)	Type of study	Variants of Concern	Results
3rd dose of Sinovac’s CoronaVac	Humans, blood tests	Beta, Gamma, Delta	Wang (Sept 5)
3rd dose of Moderna’s vax, either adapted for Beta or original or multivalent (combination of original and adapted in one dose)	Humans, blood tests	Beta, Gamma, Delta	Choi (Sept 15)
3rd dose of Sanofi’s protein subunit vax (original & version adapted for Beta), after doses of that vax or their mRNA vax	Preclinical, non-human primates	Alpha, Beta, Gamma, Delta	Pavot (Sept 21)
2nd or 3rd dose of Medigen’s protein subunit vax adapted for Beta, after dose(s) of original, and 3 doses of original	Preclinical, non-primates	Alpha, Beta, Gamma, Delta	Kuo (Oct 15)
3rd dose of Sinovac’s CoronaVac	Humans, blood tests	Alpha, Beta, Delta	Yue (Oct 19)
3rd dose of Moderna, either adapted for Beta or original	Preclinical, non-human primates	Beta, Delta, Epsilon, Gamma, Iota	Corbett (Oct 21)
3rd dose of Sinopharm’s Beijing vax	Humans, blood tests	Beta, Delta, Lambda	Ju (Nov 10)
3rd dose of Pfizer	Humans, blood tests	Delta, Omicron	Basile (Dec 13)
2 or 3 doses of Pfizer, 1 dose of J&J, or 1 or 2 doses of Moderna	Humans, blood tests	Omicron	Schmidt (Dec 13)
2-dose course of Moderna followed by half-dosage Moderna	Humans, blood tests	Beta, Omicron	Doria-Rose (Dec 20)
3rd dose of Moderna in half and full dosages, original, adapted for Beta or Omicron, or multivalent	Humans, blood tests	Omicron	Moderna press release (Dec 20)
2-dose course of Sputnik V (Sputnik Light [rAd26-S] followed by second Sputnik V vaccine [rAd5-S]), followed by another dose of Sputnik Light	Humans, blood tests	Omicron	Dolzhikova (Dec 21)
3rd dose of Moderna or Pfizer in people with multiple sclerosis on anti-CD20 treatment	Humans, blood tests	Delta, Omicron	Madelon (Dec 21)
2 doses of Novavax followed by a 3rd dose	Humans, blood tests	Delta, Omicron	Novavax press release (Dec 22)
2-dose courses of Moderna or Pfizer or single-shot J&J; additional mRNA vax (as 3rd after mRNA or 2nd after J&J), either homologous or heterologous	Humans, blood tests	Delta, Omicron	Garcia-Beltran (December 23)
3 doses of Pfizer	Humans, blood tests	Delta, Omicron	Hoffmann (Dec 23)
3rd dose of Pfizer	Humans, blood tests	Delta, Omicron	Ariën (Dec 24)
2 or 3 doses of Pfizer	Humans, blood tests	Delta, Omicron	Lusvarghi (Dec 28)
2-dose course of AZ, Moderna or Pfizer or single-shot J&J; dose of Pfizer after 2-dose Moderna or single-shot J&J	Humans, blood tests	Beta, Delta, Omicron	GeurtsvanKessel (Dec 29) (Feb 4)
2-dose course of CoronaVac followed by a dose of Pfizer	Humans, blood tests	Delta, Omicron	Perez-Then (Dec 29)
2-dose course of AZ, Moderna or Pfizer; 3rd dose of Pfizer after AZ, Pfizer or Moderna 2-course; 3rd dose of Moderna after AZ 2-course; Moderna or Pfizer dose after single-shot J&J	Humans, blood tests	Omicron	De Marco (Dec 30)
2-dose course of Pfizer followed by 3rd dose of J&J or Pfizer	Humans, blood tests	Omicron	Tan (Dec 30)
2-dose courses of Pfizer or Moderna or 3rd dose of Moderna or Pfizer	Humans, blood tests	Beta, Omicron	Carreño (Dec 31)
2-dose course of Moderna or Pfizer or single-shot J&J; booster dose of Moderna or Pfizer	Humans, blood tests	Delta, Omicron	Saharia (Jan 1)
3-dose course of AZ or Pfizer	Humans, blood tests	Alpha, Beta, Gamma, Delta, Omicron	Dejnirattisai (Jan 3)
2-dose course of AZ, Moderna, or Pfizer; 2-dose course of AZ or Pfizer with 3rd dose of Moderna or Pfizer	Humans, blood tests	Alpha, Delta, Omicron	Willett (Jan 3)
2-dose courses of AZ, Moderna and/or Pfizer with 12-week interval; 2-dose course of Pfizer with short interval with 3rd dose of Moderna or Pfizer	Humans, blood tests	Delta, Omicron	Belik (Jan 5)
2-dose courses of CoronaVac or Sinopharm Beijing with 3rd dose of either Moderna or Pfizer	Humans, blood tests	Beta, Delta, Omicron	Zuo (Jan 6)
2-dose courses of AZ or Pfizer with third dose of Pfizer	Humans, blood tests	Delta, Omicron	Faustini (Jan 8)
1 to 3 doses of Moderna or Pfizer	Humans, blood tests	Beta, Delta, Omicron	Banerjee (Jan 13)
2 doses of J&J; 2 doses of Moderna with 3rd half- or full-dose Moderna; 3 doses of Pfizer; 2 doses of Pfizer with 3rd dose of J&J; 1 dose of J&J with Pfizer 2nd dose	Humans, blood tests	Omicron	Lyke (Jan 14)
2-dose course of Sinopharm Beijing; 3-dose course of Sinopharm Beijing or 3rd dose of ZF2001	Humans, blood tests	Omicron	Wang (Jan 15)
2-dose course of Moderna or Pfizer with 3rd dose of Moderna or Pfizer	Humans, blood tests	Omicron	Jergovic (Jan 16)
3-dose course of Pfizer	Humans, blood tests	Beta, Delta, Omicron	Muik (Jan 18) (by BioNTech/Pfizer)
2-dose course of CoronaVac or AZ, or 3-dose course of AZ	Human, blood tests	Alpha, Beta, Delta, Omicron	Suntronwong (Jan 18)
3-dose courses of Moderna or Pfizer	Human, blood tests	Beta, Delta, Omicron	Walls (Jan 19)
3-dose course of Pfizer	Human, blood tests	Omicron	Wu (Jan 19)
2- and 3-dose courses of Pfizer	Human, blood tests	Omicron	Xia (Jan 22)
2-dose courses of AZ or Pfizer, 3rd dose Pfizer (people with cancer)	Human, blood tests	Omicron	Fendler (Jan 25)
2-dose course of Pfizer, 3rd dose Pfizer (longitudinal study)	Human, blood tests	Alpha, Beta, Gamma, Delta, Omicron	Wratil (Jan 28)
2-dose course of Moderna or Pfizer, 3rd dose of same (longitudinal study of healthcare workers)	Human, blood tests	Beta, Delta, Omicron	Debes (Jan 31)
2-dose course of Moderna, 3rd dose of Moderna or Moderna adapted for Omicron	Preclinical, non-human primates	Omicron	Gagne (Feb 4)
2-dose course of Pfizer or 1-dose J&J, 3rd dose of Pfizer or J&J	Preclinical, non-human primates	Delta, Omicron	Chandrashekar (Feb 7)
2-dose course of Moderna or Pfizer, 3rd dose of Moderna or Pfizer	Human, blood tests	Omicron (BA1, BA2)	Iketani (Feb 9)
2-dose course of Moderna, 3rd dose of Moderna or Moderna adapted for Omicron	Preclinical, mice	Omicron	Ying (Feb 9)
2-dose course of Moderna or Pfizer, 3rd dose of same vaccine (people who had breakthrough infections)	Human, blood tests	Delta, Omicron	Gaebler (Feb 11)

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