What’s in a COVID vaccine?

You may have heard a lot about how COVID vaccines work over the past years, and how they are being rolled out. But scroll through a list of the vaccine ingredients, and you’ll see a long list of names that aren’t helpfully labelled with their purpose. Some might be familiar, but plenty will seem foreign and difficult to pronounce.

Vaccines are made of an active ingredient (the thing that provokes an immune response) and excipients (extra ingredients, which are there to assist the active ingredient in some way). Excipients could be stabilising the active ingredient, helping it get to the right spot in the body, preventing contamination, assisting with mixing, or a combination of all of these.

Most of the excipients have been approved food and pharmaceutical products for years because it’s a lot faster to test a new vaccine, and get it approved, if most of the components have already been used in people.

Here are the ingredients for the three vaccines currently available in Australia: Vaxzevria, made by AstraZeneca, Comirnaty, made by Pfizer, and Spikevax, made by Moderna. At the end of this article, we also explain the ingredients in the Novavax vaccine, Nuvaxovid, which has been approved by the TGA and which the government has ordered 51 million doses of. As more vaccines are approved and ordered, we’ll update this list.

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Pfizer-BioNTech

Ingredients:

• BNT162b2 [mRNA]
• ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)(ALC-0315)
• 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)
• distearoylphosphatidylcholine (DSPC)
• cholesterol
• potassium chloride
• monobasic potassium phosphate
• sodium chloride
• dibasic sodium phosphate dihydrate
• sucrose
• water for injections

Active ingredient

• messenger ribonucleic acid – BNT162b2 [mRNA]

This is the famous mRNA, or messenger RNA, which the body uses to make coronavirus spike proteins, triggering an immune response that should protect you against the real coronavirus. Interestingly, Pfizer’s mRNA is slightly different to naturally occurring mRNA – it’s been nucleoside-modified, which means one of the ‘coding’ bases, uracil, has been swapped out for a molecule with a similar, but not identical, shape. This is a trick discovered more than 15 years ago – it stops the immune system from recognising and destroying the foreign mRNA before it can be used to make spike proteins.

Lipid nanoparticle coatings

• ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315)
• 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)
• distearoylphosphatidylcholine (DSPC)
• cholesterol

In order to make spike proteins, the mRNA has to get inside our cells, and our cells have oily membranes that repel molecules like mRNA. This is why the vaccine has four different lipids (long, fatty molecules that are more similar to cell membranes) coating the mRNA. They form nanometre-sized blobs, and are hence known as ‘lipid nanoparticles’.

Pfizer’s combination of lipids has been developed by a company called Acuitas, which has been researching different combinations of lipids for therapeutics for the past decade.

This combination of four different lipids has been judged by Pfizer and Acuitas to be most effective at getting the mRNA into cells. Three of the lipids (ALC-0315, ALC-0159 and DSPC) are synthetically designed, and had previously been used in a few therapeutic treatments, while the fourth (cholesterol) is a molecule of which our bodies already contain several grams.

Buffers

• potassium chloride
• monobasic potassium phosphate
• sodium chloride
• dibasic sodium phosphate dihydrate

The mRNA in the vaccine – and indeed, the molecules in our bodies – are remarkably sensitive to acidity, or pH. Salts are added because they can act as pH buffers, preventing a solution from becoming too acidic or basic. The four salts in the Pfizer vaccine are designed to keep the pH consistent over time. Two of the salts (monobasic potassium phosphate and dibasic sodium phosphate dihydrate) are also used in some pharmaceutical treatments, as well as fertilisers and as food additives, while potassium chloride and sodium chloride (table salt) are common, naturally occurring substances.

Stabilising sugar

• sucrose

Sucrose (sugar, identical to commercial white sugar) has been added to the vaccine to keep other ingredients stable, particularly as it’s stored at low temperatures.

A solvent

• water

Finally, these ingredients all need to occur in liquid form, so a vaccine needs something to dissolve and mix them. Fortunately, water is the perfect molecule to do this, which is why it’s the final addition to the vaccine.

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Oxford-AstraZeneca

Ingredients:

• 5 x 1010 ChAdOx1-S (recombinant) viral particles
• L-histidine
• L-histidine hydrochloride monohydrate
• magnesium chloride hexahydrate
• polysorbate 80
• ethanol
• sucrose
• sodium chloride
• disodium edetate dihydrate
• water for injection

Active ingredient

• 5 x 1010 ChAdOx1-S (recombinant) viral particles

This is the ‘viral vector’ that makes the Oxford-AstraZeneca vaccine a ‘viral vector’ vaccine. It’s a tame virus (an adenovirus, not a coronavirus) that contains DNA to make SARS-CoV-2 spike proteins, which will trigger your immune system.

The adenovirus has been modified so that it can’t replicate or harm people. It’s modelled on an adenovirus originally found in a chimpanzee, though no chimpanzees have been involved in the production of this vaccine. Instead, it’s grown in lab-based cells, which have been grown from cells originally taken from a human kidney, then genetically modified. In Australia, the viral growing is done in Melbourne.

Because AstraZeneca’s active ingredient comes with its own coating package in the form of an adenovirus, it doesn’t need lipids like the Pfizer vaccine. It does, however, need molecules to buffer the pH and keep it stable – as well as a couple of preservatives.

Buffers

• L-histidine
• L-histidine hydrochloride monohydrate
• magnesium chloride hexahydrate
• sodium chloride

Like the Pfizer vaccine, salts (magnesium chloride hexahydrate and sodium chloride) and amines (L-histidine and L-histidine hydrochloride monohydrate) are added to keep the pH consistent.

Both salts are naturally occurring minerals, while L-histidine is a molecule known as an amino acid. These compounds are what our proteins are made of, so there’s already plenty of L-histidine inside you. L-histidine hydrochloride monohydrate is similar to histidine (hence the name), and it’s also been used in foods, cosmetics and soaps.

Emulsifier

• polysorbate 80

Oily things (like the outsides of adenoviruses) and watery things don’t mix well together, so the AstraZeneca vaccine requires an emulsifier to combine them. An emulsifier is a molecule that has both hydrophobic (oily) and hydrophilic (watery) sections, allowing them to mix – detergents and soaps are a common example; the lecithin in egg yolks is another.

Polysorbate 80 is a common food additive because of its emulsifying properties, and it’s also been used in other, non-COVID, vaccines.

Preservatives

• ethanol
• disodium edetate dihydrate

While it’s kept in very sterile conditions, the AstraZeneca vaccine still uses preservatives to prevent any sort of contamination from the vials or manufacturing process. (Pfizer has opted to avoid preservatives, which means the vaccine requires fewer ingredients, but some doses have been discarded because they can’t be guaranteed non-contaminated.)

As well as being a preservative, disodium edetate dihydrate (EDTA) is an approved medication for treating some types of metal poisoning.

The ethanol is identical to the alcohol you get in hand sanitiser, beer and wine, but at a concentration of less than 0.005% in a 0.5-millimetre dose, it’s not going to affect your blood alcohol content.

Other ingredients

• sucrose
• water

As with the Pfizer vaccine, sugar is used to stabilise the ingredients, and water is used to combine all the ingredients.

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Moderna

Ingredients:

• messenger ribonucleic acid (mRNA)
• SM-102
• polyethylene glycol [PEG] 2000 dimyristoylglycerol [DMG]
• cholesterol
• distearoylphosphatidylcholine (DSPC)
• tromethamine
• tromethamine hydrochloride
• acetic acid
• sodium acetate trihydrate
• sucrose
• water

Active ingredient

• messenger ribonucleic acid (mRNA)

As with the Pfizer vaccine, the Moderna vaccine primes the immune system with mRNA. Moderna’s mRNA is also slightly different to naturally occurring mRNA (nucleoside-modified), so that it doesn’t trigger the immune system at the wrong point.

Lipid nanoparticle coatings

• SM-102
• polyethylene glycol [PEG] 2000 dimyristoylglycerol [DMG]
• distearoylphosphatidylcholine (DSPC)
• cholesterol

Like the Pfizer vaccine, the mRNA in the Moderna vaccine needs an oily coating to allow it to get into cells, and once again, lipids are the key.

Two of the lipids used – DPSC and cholesterol – are identical to those in Pfizer’s vaccine. (In Moderna’s documentation, DSPC is referred to as 1,2-distearoyl-sn-glycero-3-phosphocholine rather than distearoylphosphatidylcholine, but it’s the same molecule, with a different, equally unpronounceable name.)

The other two lipids are synthetically designed. While the lipid nanoparticle combination has been in development and testing for years, Moderna is currently in a legal battle with a smaller company, Arbutus, over patents on the specific combination of lipids – Moderna has lost one patent challenge, but it’s uncertain if that entitles Arbutus to royalties from any profit Moderna makes on the vaccine (or other products). So the credit for developing them is unclear, but two companies at least have spent a lot of time and funds on them.

Buffers

• tromethamine
• tromethamine hydrochloride
• acetic acid
• sodium acetate trihydrate

As with other vaccines, buffers are used to maintain the pH.

Tromethamine and tromethamine hydrochloride are very common buffers in chemical research, while you’re probably most familiar with acetic acid as a component of vinegar. Sodium acetate trihydrate (very similar to acetic acid) is another very common food additive.

Other ingredients

• sucrose
• water

As with the other vaccines, sugar and water are added to stabilise and mix the components.

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Novavax

Ingredients:

• SARS-CoV-2 rS (NVX-CoV2373)
• Matrix-M adjuvant, which contains:
  • Quillaja Saponaria saponins fraction A
  • Quillaja Saponaria saponins fraction C
  • cholesterol
  • phosphatidylcholine
  • monobasic potassium phosphate
  • potassium chloride
• Dibasic sodium phosphate heptahydrate
• Monobasic sodium phosphate monohydrate
• Sodium chloride
• Polysorbate 80
• Sodium hydroxide
• Hydrochloric acid
• Water

Active ingredients

• SARS-CoV-2 rS (NVX-CoV2373)
• Polysorbate 80

The Novavax vaccine – Nuvaxovid – uses neither an adenovirus vector or mRNA: it’s called a protein subunit vaccine. It adds SARS-CoV-2 spike proteins which have been grown in lab-based insect cells (from the fall armyworm moth), then purified.

Without a virus to support them, SARS-CoV-2 spike proteins would fall apart in the vaccine vial or in the body, before the immune system had time to recognise them. But Novavax has figured out a way to keep them stable: when mixed with polysorbate 80, the proteins arrange themselves into nanometre-sized ‘rosettes’, with polysorbate 80 at the core keeping them together. These nanoparticles then last in a vaccine vial for much longer.

Polysorbate 80 has appeared in other vaccines on this list as an emulsifier – it’s a very common food additive.

Adjuvant

• Matrix-M1 adjuvant, which contains:
  • Quillaja Saponaria saponins fraction A
  • Quillaja Saponaria saponins fraction C
  • cholesterol
  • phosphatidylcholine
  • monobasic potassium phosphate
  • potassium chloride

The other thing Novavax relies on is an adjuvant: a substance that increases the immune response to the active ingredient. Lots of vaccines use adjuvants, but it’s not always clear how they work – there are thought to be a few different mechanisms.

Novavax’s adjuvant, Matrix-M, is made of particles 40 nanometres in length. The particles are based on substances called saponins, which have been extracted from the soap bark tree (Quillaja Saponaria). These are the two Quillaja Saponaria compounds on the list. Saponins have been used as food and cosmetics additives for a while, along with being a source of interest for their adjuvant properties.

The other ingredients in the adjuvant are there to keep the saponins in stable nanoparticles. Cholesterol, monobasic potassium phosphate, and potassium chloride all appear further up this list in other vaccines, while phosphatidylcholine is a naturally occurring lipid. It’s chemically similar to distearoylphosphatidylcholine, which also appears further up this list in the Pfizer and Moderna vaccines.

Buffers

• Dibasic sodium phosphate heptahydrate
• Monobasic sodium phosphate monohydrate
• Sodium chloride
• Sodium hydroxide
• Hydrochloric acid

As with the other vaccines, the Novavax vaccine requires compounds to keep its pH stable. Three salts – dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate, and sodium chloride – do a lot of the work here.

Sodium chloride (table salt) is a familiar name, but the other two sodium salts here are actually very similar to each other, and to dibasic sodium phosphate dihydrate in the Pfizer vaccine. All three are combinations of sodium, phosphate, and water, and all three are common pharmaceutical additives.

Sodium hydroxide and hydrochloric acid are both names that may alarm you a bit: in high concentrations, both can be very corrosive. But in this vaccine, they’re both only present in extremely small amounts, and they’re there to tune the pH: sodium hydroxide, being basic, can raise it, while hydrochloric acid, being acidic, can lower it. When both present, they’ll cancel each other out, creating more buffer solution.

Other ingredients

• water

As with the other vaccines, Novavax uses water to mix all these components.

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If you’d like to know more about the development of (and ingredients in) vaccines, we’ve published a piece on it in Cosmos 92 – read an excerpt here.

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