The Covid-19 Vaccine Explained

Feb 26, 2021

Health & Lifestyle | Lauranne Heres

Since the beginning of the Covid-19 pandemic, the world has waited for a way out. Anything to end the lockdowns, the travel bans, and most of all, something to prevent millions dying worldwide. While there are now some medications known to alleviate the worst symptoms, and helping severe Covid patients to leave the hospital, we’re still far from a cure. And so, the vaccine, which is meant to prevent infection and help avoid severe Covid, is so far the only viable solution to slow down the spread and reduce the patient load in hospitals around the globe. Yet the vaccines (since there are many different ones being manufactured) are at the heart of a new controversy. The growing numbers of anti-vaxxers in countries such as the USA, France, Ukraine and Pakistan just to name a few has led to much distrust when it comes to the new vaccines, especially because they were manufactured quickly in response to the pandemic. Dr Hadrien Peyret, a postdoctoral researcher at the John Innes Centre in Norwich, specialises in virology and virus-based biotechnologies. He completed his PhD on a novel method to design vaccines in 2014 and will answer some of the most common questions about the new anti-Covid vaccines.

“Since these vaccines were made so quickly, we don’t know how safe they are, and we won’t know the long-term side effects for quite some time. How can we be sure it’s ok to take them?”

It is true that we can’t know the long-term side effects of these vaccines beyond the amount of time elapsed since they have been tested: in this case the anti-Covid vaccines currently in use were first tested on humans in late spring of 2020, meaning by definition we only have data on safety for whatever time has elapsed since then (currently about 10 months). But it’s important to consider that by far the biggest risk with vaccines (any vaccine, regardless of technology) is very short-term issues, notably serious allergic reactions such as anaphylaxis. The ingredients that make up the vaccine don’t hang around your body for ever, they are cleared within a few days, leaving only the immune memory behind, so the more time has elapsed since vaccination, the lower the risk. And the short-term risks are extremely well documented. There are publicly-available peer reviewed scientific publications on phase 1, phase 2 and phase 3 clinical trials carried out on tens of thousands of people that report all manner of “adverse events”, whether it’s the BioNTech/Pfizer vaccine (phase 3 trial here), or the one made by Moderna (phase 3 trial here), or Oxford/AstraZeneca (phase 3 trial here), or even the Russian Sputnik V vaccine (phase 3 trial here), mostly a sore arm after the injection, and sometimes headaches and fever that last a day or two. Also, and perhaps more importantly, this question sounds very sensible but it’s also a classic case of a cognitive bias known as the omission bias. This is when we (falsely) assume that not doing a particular action (such as getting vaccinated) is fundamentally more cautious and carries less risk than carrying out said action. This is because our human brains are particularly bad at estimating the risks that we are subjecting ourselves to by simply going about our daily lives. In the case of Covid vaccines, it might feel safer to “not risk the vaccine” but implicitly in that decision we are making an active choice to risk Covid-19 itself. And the risks of Covid-19 (both short term and longer term for those who end up with so-called “Long Covid”) are demonstrably high and serious. So, the more logical way to think about this isn’t to weigh the perceived unknown risks of a vaccine against nothing, but rather to compare the known risks of the vaccines with the known risks of getting Covid-19. Taking a look around at our lives since the pandemic began, the decision is a no-brainer.

“I know someone who got the vaccine and then got sick just after having it. They say the vaccine gave them coronavirus. Is that true?”

What almost certainly happened in this situation is that the person in question caught the virus a couple of days before getting vaccinated. From what we know at the moment (nicely summarised in this review article in the British Medical Journal), on average, a person won’t show symptoms until about 5 days after having been infected with the virus (but will start to be contagious before showing symptoms). It’s important to note that it is literally physically impossible for the anti-Covid vaccines currently in use in the UK, Europe and the US to give you coronavirus. RNA vaccines (such as the BioNTech/Pfizer, Moderna, and CureVac products) or viral vector vaccines (such as the Oxford/AstraZeneca, Sputnik 5, Jannsen/J&J, or CanSino products) do not contain infectious virus, and in fact are produced without ever using infectious virus at any point in the production process. They use only the bit of the viral genome that codes for the Spike surface protein, which is about 15% of the genome, and does not include any of the important bits needed for the virus to replicate. Note however that this is technically not the case for two vaccine candidates developed in China: BBIBP-CorV, produced by Sinopharm, and CoronaVac, produced by SinoVac. These two vaccines are whole virus inactivated vaccines, which means the infectious SARS-CoV-2 virus is grown up in huge vats of cells, purified, then rendered inactive (or “killed”) by a chemical treatment. This is an older vaccine technology that we have been using for decades to make our rabies and polio vaccines, for example. Even though this inactivation process is very well established and every vaccine lot will be checked rigorously in a quality assurance process, it is technically possible that some vials of these vaccines could contain incompletely inactivated virus. But even with these vaccines (used in some parts of the world including China and the United Arab Emirates), in the context of a pandemic you are overwhelmingly more likely to catch the virus from a work colleague or family member the day before your vaccination appointment than you are to catch the virus from the vaccine itself.

“How do the different vaccines work? Which one works best? Why can’t I chose what I get?”

There are 4 main types of vaccines being used (or soon to be used) against SARS-CoV-2. The Nature website has a very helpful and nicely illustrated guide here.

· The first type in use at the moment are RNA vaccines (BioNTech/Pfizer and Moderna are currently in use, CureVac probably will be later this year). These consist of lipid (fat) nanoparticles that contain a short molecule of specially designed RNA. The lipid nanoparticle is really just there to help the RNA get into your cells when the vaccine is jabbed into your arm: it’s the RNA that’s the really important bit: this molecule provides genetic instructions to your cells to produce the coronavirus Spike protein. Specifically, this will mostly take place in types of cells called “antigen presenting cells”: these are cells that form part of your immune system that will be drawn to the injection site in your shoulder when you get vaccinated. Once on site, the lipid nanoparticles will deliver the RNA to these cells and the cells will follow those genetic instructions to start producing lots and lots of coronavirus spike proteins, which will then do what it naturally does and stick out of the surface of these cells, where it will be detected by other types of cells in your immune system. To your immune system, this will look exactly like a sudden viral infection, and it will respond by producing antibodies and other immune responses geared towards recognising that spike protein, and destroying anything that this protein is stuck to, whether that be virus particles or infected cells. So if and when you are exposed to SARS-CoV-2, your body will very quickly recognise it (thanks to that spike protein on its surface) and destroy any particles it finds in your body, as well as any cells that the virus has managed to infect. This recognition and response will happen so quickly that the infection will never really take hold, and you probably won’t ever show any symptoms.

· Viral vectored vaccines (Oxford/AstraZeneca and Gamaleya Sputnik V vaccines are currently in use, and the Janssen/Johnson&Johnson will probably be later this year) actually work in a remarkably similar way to the RNA vaccines. The key difference is the delivery vehicle: instead of delivering the genetic information to produce the spike protein via RNA in a lipid nanoparticle, these vaccines use DNA packaged inside a “disabled” adenovirus: a completely different type of virus that’s very easy to work with and render non-infectious (and therefore harmless), but still capable of delivering its DNA to your cells. And in this case, the adenovirus DNA has been modified to include instructions for making the coronavirus spike protein, so this modified adenovirus is used as a “vector” for introducing the genetic instructions for the coronavirus spike proteins to your cells (hence the name). Everything from that point on is exactly the same as for RNA vaccines.

· Protein-based vaccines (Novavax has announced very promising clinical results and is likely to be approved before this summer, with others like Medicago a couple of months behind that) on the other hand work a bit differently. Instead of providing your cells with instructions on making the Spike protein (thereby mimicking your cells being infected), protein-based vaccines involve injecting the Spike protein straight into your arm, mimicking the presence of virus particles. In some cases (like the Novavax vaccine), the Spike protein is mostly just on its own or stuck to a couple of other copies of the spike protein (we call these “subunit” vaccines). In other cases (such as Medicago’s vaccine), the Spike protein is actually on the surface of a “virus-like particle”, which consists of many copies of the Spike protein sticking out of a lipid membrane just like in the real SARS-CoV-2, but without any infectious coronavirus genome inside (and therefore totally harmless). These vaccines make your immune system believe that a load of virions (virus particles) have just invaded your body, and so will trigger an immune response to destroy these proteins and build up an immune memory of this spike protein in order to recognise it should it ever be seen in your body again (i.e. if you then get exposed to SARS-CoV-2).

· Inactivated virus vaccines (such as BBIBP-CorV, produced by Sinopharm, and CoronaVac, produced by SinoVac; both currently in use in a few countries but not at this time approved by regulators in the US, UK, or EU) are different again. These consist of actual SARS-CoV-2 virus that has been grown up in large vats of cells then purified and “inactivated” by chemical treatment to make it incapable of causing an infection. Once injected into your arm, your body doesn’t know that it is inactivated (just like it doesn’t know that the protein-based vaccines are just non-infectious protein) and so it just treats these virus particles as invading pathogens that need to be destroyed and remembered as “immune memory” in case of future attack.

It’s extremely difficult to know at the moment which vaccine works “best”, for two reasons. The first is that none of these vaccines have been used for long enough for us to have enough good data to identify one or two stand-out “winners”. That may come within a few months. The other major reason is that is that there are actually many different ways of comparing these vaccines. Most phase 3 clinical trials specifically measured efficacy against symptomatic Covid-19: that means that the headline numbers you’ve heard such as “the Moderna vaccine is 95% effective” means that in placebo-controlled trials (in this example, this one here), 95% of trial volunteers who developed Covid-19 symptoms and tested positive were in the placebo group, and only 5% were in the vaccinated group. But that’s any symptoms that led these volunteers to get tested, however mild. This doesn’t tell you much about efficacy against severe disease (when you need to be given extra oxygen in hospital) or death from Covid-19. It looks so far like all of these vaccines are highly effective at preventing severe disease and death from Covid-19. We also don’t yet know what (if any) differences there are between the vaccines in terms of how much they prevent vaccinated people from spreading SARS-CoV-2 if they do get infected after vaccination. We are starting to get some indications that some of these vaccines do reduce the risk of transmission (for example in this new study about the Oxford/AZ vaccine: and this one about the BioNTech/ Pfizer jab), but it’s still not clear exactly by how much or how the vaccines compare in this regard. We will almost certainly know more about this in the coming months.

In many countries you can’t chose which vaccine you get mainly because we are at the beginning of the single biggest mass vaccination campaign in the history of medicine, with every government and healthcare official desperate not to waste a single dose as they ration out limited supplies in a complicated process of prioritisation. Adding people’s personal preferences would make everything vastly more complicated, and is completely unnecessary: regulatory agencies such as the FDA in the US, the MHRA in the UK and the EMA in the EU specifically authorise vaccines for use because they have looked at all the data and concluded that they are safe and that they work. If your national health regulator has authorised a vaccine for use and your doctor has arranged for you to have it, take it. You should get the first approved vaccine that you’re offered by your doctor.

“We’ve been told we’ll probably have to get booster vaccines every year, much like with the flu. How likely is that scenario?”

I get a bit annoyed at this kind of oversimplistic message that I’ve seen relayed in the press. This comes from two quite different potential problems with the vaccination campaign, and the flu analogy is a bit weak in both cases. I’ll try to explain as best I can.

· The first context in which journalists say this kind of thing is when we’re talking about how long vaccine protection will last. For months, before we had results of large-scale clinical trials, scientists were (correctly) cautioning that even if vaccines turn out to work (i.e. offer protection from Covid-19 disease), we won’t know immediately how long that protection lasts. These scientists would then go on to explain (correctly) that, in a worst-case scenario in which vaccine protection only lasts for a few months, we could always give people another dose (a “booster”) every few months. The analogy with the flu vaccine is that giving everyone a booster every few months is doable, and we know that because we give loads of people a fresh flu vaccine (not a booster) every year. This was basically scientists trying to explain a potential problem that we might face even with vaccines that work, but why such a problem isn’t necessarily that big a deal in the grand scheme of things. My feeling is that journalists then took this flu analogy and basically turned it into “SCIENTISTS SAY WE’LL NEED BOOSTER JABS EVERY YEAR JUST LIKE FLU”. In reality, we still don’t know how long vaccine protection lasts exactly, but so far there is nothing to make us think that protection only last a few months.

· The second context in which this comes up is when we’re discussing variants. Here we have a similar situation to the first, in which scientists try to explain that in the worst-case scenario, one or a few of the vaccines might not work well enough against a new variant. And again, the scientists then go on to explain that in the grand scheme of things this wouldn’t be a complete catastrophe because we could just tweak the formulation of the vaccines to make them work well against these new variants. And again, we know that this is doable because that’s what we do with the flu vaccines every year. And again, this somehow became “SCIENTISTS SAY WE’LL NEED BOOSTER JABS EVERY YEAR JUST LIKE FLU”. In reality, it’s looking like some vaccines still work very well against all current variants (even if they work slightly less well against some compared to others), and those that don’t can either be tweaked or relevant countries can just use the ones that still work well enough instead. Coronaviruses are very different to influenza viruses: influenza viruses mutate and evolve far (far!) faster than coronaviruses, and once most people are vaccinated it seems unlikely to me that new variants of SARS-CoV-2 that require a new vaccine formulation would appear as often as every year. The measles virus has been circulating for decades since we developed a vaccine against it, and we’ve never had to change our vaccine formulation against that. Depending on where you live, when you get vaccinated, and what vaccine you get, you might get one “variant booster” a few months after your second jab, but honestly I’d be surprised if you need any more after that. That being said if vaccines don’t get into the arms of many of the 3 billion people in poorer countries within the next year, these places could become breeding grounds for new variants for years to come, and then all bets are off.

“I’ve heard of people having allergic reactions to the vaccine. How often is this happening? Do we have to worry?”

By and large, you probably don’t need to worry about this. If you are not particularly prone to having allergic reactions, then this is quite an unlikely occurrence. The EU medicines regulator (the EMA) says on its information page about the BioNTech/Pfizer vaccine the following: “Allergic reactions (hypersensitivity) have been seen in people receiving the vaccine. A very small number of cases of anaphylaxis (severe allergic reaction) have occurred since the vaccine started being used in vaccination campaigns. Therefore, as for all vaccines, Comirnaty should be given under close medical supervision, with the appropriate medical treatment available. People who have a severe allergic reaction when they are given the first dose of Comirnaty should not receive the second dose.” In this report by the EU’s EMA about safety of the BioNTech/Pfizer vaccine, you can see that it is estimated that anaphylaxis is estimated to occur in 11 people out of every million doses administered. That’s a 0.0011% chance. The American CDC has an even more detailed report into allergic reactions (anaphylaxis and less severe allergic reactions) regarding the BioNTech/Pfizer vaccine here. You can see that allergic reactions are, on the whole, incredibly rare, and quite easily treated when they do occur. If you dig around on google, you can find the same documents about the Moderna vaccine from the EMAand from the CDC which also show very low rates of allergic reactions and extremely low rates of anaphylaxis (2.5 cases per million doses). The Oxford/AstraZeneca vaccine hasn’t been used for long enough for there to be any “real world” safety reports from the EU yet, and of course it hasn’t been authorised in the US yet, but you can also find the UK government’s assessment of allergic reactions and other side effects for the Oxford/AstraZeneca vaccine (along with the BioNTech/Pfizer vaccine) here in which it states: “The MHRA also closely monitors reports of anaphylaxis or anaphylactoid reactions with the AstraZeneca vaccine. These are reported less frequently than with the Pfizer/BioNTech vaccine, with 60 UK spontaneous adverse reactions associated with anaphylaxis or anaphylactoid reactions reported and is very rare. An update to the product information has been made to reflect the fact that cases of anaphylaxis have been reported for the AstraZeneca vaccine.” Generally speaking, if you are particularly prone to severe allergic reactions (for example if you carry an epinephrine autoinjector such as an EpiPen around with you) then this is something that you will want to discuss with a doctor before being vaccinated, and in fact it’s likely that whoever is vaccinating you (a nurse or doctor) will ask you about this before proceeding with the vaccination. In most countries, healthcare professionals carrying out vaccinations are specially trained to deal with anaphylaxis, the severe response that can occur after an allergic reaction to a vaccine. Anaphylaxis is typically only life-threatening if you don’t get medical attention very quickly, but the person who vaccinates you will have all the expertise and material needed to treat you immediately if this does occur.

“What kind of side effects should we realistically expect from any Covid vaccine?”

· Here is what the EMA says about the BioNTech/Pfizer vaccine: “The most common side effects with Comirnaty [The brand name for the BioNTech/Pfizer vaccine] in the trial were usually mild or moderate and got better within a few days after vaccination. These included pain and swelling at the injection site, tiredness, headache, muscle and joint pain, chills, and fever. They affected more than 1 in 10 people. Redness at the injection site and nausea occurred in less than 1 in 10 people. Itching at the injection site, pain in the limb, enlarged lymph nodes, difficulty sleeping and feeling unwell were uncommon side effects (affecting less than 1 in 100 people). Weakness in muscles on one side of the face (acute peripheral facial paralysis or palsy) occurred rarely in less than 1 in 1,000 people. Allergic reactions have occurred with Comirnaty, including a very small number of cases of severe allergic reactions (anaphylaxis) which have occurred when Comirnaty has been used in vaccination campaigns. As for all vaccines, Comirnaty should be given under close supervision with appropriate medical treatment available.”

· And here’s what they say about the Moderna vaccine: “The most common side effects with Covid-19 Vaccine Moderna in the trial were usually mild or moderate and got better within a few days after vaccination. They included pain and swelling at the injection site, tiredness, chills, fever, swollen or tender lymph nodes under the arm, headache, muscle and joint pain, nausea and vomiting. They affected more than 1 in 10 people. Redness, hives and rash at the injection site and rash occurred in less than 1 in 10 people. Itching at the injection site occurred in less than 1 in 100 people. Swelling of the face, which may affect people who had facial cosmetic injections in the past, and weakness in muscles on one side of face (acute peripheral facial paralysis or palsy) occurred rarely, in less than 1 in 1000 people.

Allergic reactions have occurred in people receiving the vaccine, including a very small number of cases of severe allergic reactions (anaphylaxis). As for all vaccines, COVID-19 Vaccine Moderna should be given under close supervision with appropriate medical treatment available.”

· And again for the Oxford/AstraZeneca vaccine here: “The most common side effects with Covid-19 Vaccine AstraZeneca in the trials were usually mild or moderate and got better within a few days after vaccination. The most common side effects are pain and tenderness at the injection site, headache, tiredness, muscle pain, general feeling of being unwell, chills, fever, joint pain, and nausea. They affected more than 1 in 10 people. Vomiting and diarrhoea occurred in less than 1 in 10 people. Decreased appetite, dizziness, sweating, abdominal pain and rash occurred in less than 1 in 100 people. Allergic reactions have occurred in people receiving the vaccine. As for all vaccines, Covid-19 Vaccine AstraZeneca should be given under close supervision with appropriate medical treatment available.”

And the UK government vaccine safety report up to the 7th of February concludes with this : “In clinical trials, the Pfizer/BioNTech and Oxford University/AstraZeneca Covid-19 vaccines have demonstrated very high levels of protection against symptomatic infection. We expect data to be available soon on the impact of the vaccination campaign in reducing infections and illness with Covid-19 in the UK. All vaccines and medicines have some side effects. These side effects need to be continuously balanced against the expected benefits in preventing illness. Following widespread use of these vaccines across the UK, the vast majority of suspected adverse reaction reports so far confirm the safety profile seen in clinical trials. Most reports relate to injection site reactions (sore arm for example) and generalised symptoms such as a ‘flu-like’ illness, headache, chills, fatigue, nausea, fever, dizziness, weakness, aching muscles, and rapid heartbeat. Generally, these reactions are not associated with more serious illness and likely reflect an expected, normal immune response to the vaccines. Following very substantial exposure across the UK population, no other new safety concerns have been identified from reports received to date, and for the cases of other medical conditions reported in temporal association with vaccination, the available evidence does not currently suggest that the vaccine caused the event. The overall safety experience with both vaccines is so far as expected from the clinical trials. The expected benefits of the vaccines in preventing Covid-19 and serious complications associated with Covid-19 far outweigh any currently known side effects. As with all vaccines and medicines, the safety of Covid-19 vaccines is a continuously monitored and benefits and possible risks remain under review.”

“I’ve heard that in Norway, old people are dying after the vaccine. Should they be vaccinated at all?”

There were reports from Norwegian care homes about very elderly people dying soon after being given the BioNTech/Pfizer vaccine. This is fundamentally quite tricky to study, because of course very elderly people die in nursing homes all the time, so it’s often pretty difficult to ascribe these deaths to a single event or cause. However, regulators across the world have concluded that these reports do not justify changing guidelines for vaccination of elderly people. You can go on the Norwegian Medicine Agency (NOMA)’s website and look at their weekly adverse reactions reports here. If you download the one from the week of January 21st, you can see their assessment: “Many of the nursing home residents who have been vaccinated so far are very frail or terminally ill patients. Every day, an average of 45 people die in Norwegian nursing homes or other similar institutions. The fact that some nursing home residents die soon after being vaccinated does not imply that there is a causal relationship. The reported deaths have occurred within a period of 1-9 days following vaccination. In several of the fatal reports, the reporter states that no link with vaccination is suspected, and that the death is being reported for the sake of completeness. Many of the patients were also frail prior to vaccination. However, in the case of some of the frailest patients, it cannot be ruled out that relatively mild adverse reactions following vaccination contributed to a more severe course in their general condition or underlying illness, leading to death of the patient. These individual case reports do not currently constitute a signal of a new adverse reaction and therefore do not provide a basis for revising the product information for the vaccine.”

Also, The EU’s EMA looked into these reports and concluded that there was no evidence that these deaths were caused by the vaccine. In this report they explain this: “Given concerns which arose from Norway about deaths reported in frail elderly individuals after vaccination with Comirnaty, PRAC reviewed the current reports of suspected side effects with fatal outcome in individuals of any age. This review did not suggest a safety concern. In many cases concerning individuals above 65 years of age, progression of (multiple) pre-existing diseases seemed to be a plausible explanation for death. In some individuals, palliative care had already been initiated before vaccination. Before Comirnaty was granted a marketing authorisation in the EU, the safety of the vaccine was carefully assessed through large clinical trials across age groups including study participants that were 75 years of age and older, as detailed in the public assessment report. PRAC concluded that based on the current data there was no need to amend the product information regarding how Comirnaty should be used, including in frail elderly individuals. PRAC requested that the marketing authorisation holder continues reviewing all reports of suspected side effects with fatal outcome thoroughly.”

“At first, we were told we’d receive the 2 doses about a month apart. Now that’s been spread out to 12 weeks. Everyone freaked out, but now it seems that a longer gap is actually better. Can you explain?”

This is actually a classic case of new data being generated constantly and informing policy even as the policy is being implemented. Remember, all those phase 3 clinical trials that gave great preliminary results back in December are not over: they are still ongoing, and they are still generating tons of new data. In the phase 3 clinical trials for the Oxford/AstraZeneca vaccine, the vaccination schedule stated that the two doses should be given between 4 and 12 weeks apart. This means that there is quite a lot of variability between thousands of trial participants in when they got their two doses, making lots of smaller sub-groups to analyse. This is actually good because it mimics real-world conditions, where you might not be able to make your second jab appointment precisely 28 days after your first. By analysing data from the ongoing trials, the research team found that protection from COVID-19 actually tended to be a bit better for people who had longer delays between the first and second dose. This data have recently been published in The Lancet. Perhaps surprisingly, they find that people who wait longer between the two jabs (up to 12 weeks) end up with better protection from Covid-19 after their second jab. This explains why the recommendation in the UK is that people can wait 12 weeks for their second Oxford/AstraZeneca jab, and many other countries are taking this into account as well. The French medicines regulator for example, changed its guidance to say that it is now “recommended” that there be a delay of 9-12 weeks between the two doses of the Oxford/AstraZeneca vaccine (in case you can read French, you can read about that on the French regulator’s website here). Note, however, that all of this is not the case for the BioNTech/Pfizer or Moderna vaccines. There is no publicly available data to suggest that protection from Covid-19 provided by these vaccines gets better by waiting longer than 3-4 weeks between the two doses. That having been said, there is no strong data to indicate that the protection gets worse by waiting 12 weeks between doses. The UK government is therefore taking a bit of a gamble extending the 12-week interval recommendation to the RNA vaccines and not just the Oxford/AZ vaccine, but their justification is that this allows the UK to give one dose to more people more quickly: they would rather have lots of half-immunised people for a couple of months than half as many fully immunised people. This is quite controversial scientifically, with some arguing that it is not evidence-based and could even backfire (such as the arguments laid out here), but the British Society for Immunology indicated that on balance it is probably an acceptable strategy. Note that the European and American regulators have not recommended an extended 12-week schedule for either the BioNTech/Pfizer or Moderna vaccines: they are sticking to 3-4 weeks between jabs.

“I saw that they’re thinking of mixing vaccines, to see if it increases efficacy. Surely that’s not legit, is it?”

Actually, there are good scientific reasons to think that this could be a good idea. Each vaccine has its strengths and weaknesses in terms of triggering different parts of the immune system. So, it is actually reasonable to think that there may be a combination of two different vaccines in which each vaccine compensates for any weakness of the other, giving an overall better protection. The idea is that you’d get the best of both worlds. The trouble is that it could also go the other way: you could get the worst of both worlds if the two vaccines don’t compensate for each other’s weaknesses. That’s why it’s very important to not just give people random jabs during the vaccination campaign, but rather to study different combinations carefully in well-designed clinical trials. These trials are starting in various countries (including the UK) and you can read more about the scientific rationale for this here.

“What happened to all the labs that couldn’t figure out their own vaccine (like Australia, France etc.), will they now be used to produce vaccines for another “brand”? Will they be given a “recipe” to try and make their own?”

The short answer is yes, loads of pharmaceutical companies that are not still developing their own promising vaccines (and there are a few of those) are getting their production facilities ready to help produce existing vaccines. French vaccine giant Sanofi has run into some big delays and issues with the vaccine candidate that it was developing with British vaccine giant GlaxoSmithKline, and is a bit slow off the mark with another vaccine candidate that they are developing with a small company called Translate Bio. Even though Sanofi isn’t giving up on these, the company recently announced that some of its production capacity is being prepared to produce the BioNTech/Pfizer vaccine, and they will probably be ready to start manufacturing this summer. Similarly, Swiss pharmaceutical giant Novartis has announced that they are in talks with BioNTech/Pfizer to help out with production of their vaccine.

“Some of the vaccines don’t seem to offer protection against these new variants we have. What’s the point in getting them then if we can still get sick?”

There is increasing evidence that the vaccines currently in use still provide protection against the variants that most people are worried about: For one thing, we are starting to get good evidence that the vaccines all still offer good protection against variant B.1.1.7, also known as the “British” or “Kent” variant (such as this study about the Oxford/AZ vaccine). The bigger concern is about variant B.1.351, aka the “South-African variant”. There is evidence to suggest that the BioNTech/Pfizer vaccine (study here) and the Moderna vaccine (study here) might work a bit less well against this variant, though they are still expected to offer substantial protection. The Oxford/AstraZeneca vaccine, however, seems to provide only about 10% protection against this variant (study here). However, the level of efficacy that we are talking about here relates to protection from symptomatic Covid-19: i.e. having symptoms that are clear enough that you get tested, and the test comes back positive. We still expect all vaccines, even the Oxford/AstraZeneca vaccine, to have substantial efficacy against severe and deadly Covid-19: i.e. disease that requires intensive care and may lead to death. We don’t know for sure yet because there haven’t been enough cases of people in the clinical trials getting infected with the South African variant and then getting seriously ill and dying for us to be able to do statistical analyses on the difference between vaccinated and placebo groups (remember, all these trials are ongoing). We do know for the next round of vaccines though: both the Novavax and the Janssen/Johnson&Johnson vaccines are reported to work quite well against the South African variant, at least as far as preventing serious disease and death is concerned. They haven’t published their results in the scientific literature yet, but you can see a nice description and analysis of what the two companies have claimed in this article from the British Medical Journal. Basically, the main takeaway from all this is that all vaccines will probably work very slightly less well against variant B.1.1.7 (the “British” variant), and will probably work much less well against variant B.1.351 (the “South-African” variant) in terms of preventing noticeable Covid-19 symptoms, but all are still expected to provide substantial protection against severe disease and death.

“I read that even if I’m vaccinated, I still have to self-isolate and get tested if I want to travel. Why is that? Surely the vaccine prevents me from having the illness, right?”

The scientific reason for this is that we don’t yet know for sure if the vaccines prevent you from spreading SARS-CoV-2 if you catch it after being vaccinated. The worst-case scenario is that while the vaccine prevents you from getting sick, it doesn’t prevent you from spreading the virus, so you could unknowingly be an asymptomatic spreader of the virus. It will take a few more weeks for us to get better data about this, but most scientists are pretty optimistic that the vaccines will probably at the very least reduce the risk of contagion quite substantially. We are already getting some data which suggests that this is the case, with the Oxford/AZ vaccine here and with the BioNTech/Pfizer vaccine here. You can read more about this subject in this article from Nature news. Until we have better data about transmission of the virus after vaccination, it’s quite sensible to be cautious and act as though those who have been vaccinated may still contribute to the spread of the virus, even if they themselves probably won’t get sick.

“Why are we not vaccinating children, or pregnant women? Surely there’s something dodgy going on?”

The short answer is that the clinical trials excluded children and pregnant women. This is quite common: clinical trials are using people as test subjects, so there’s always a limit to what sorts of people you can include. Because Covid-19 is not normally very serious among children, it was not deemed justified to use them as test subjects for the vaccines in the first instance. Also, children’s immune responses (and those of pregnant women) may be a bit different to those of non-pregnant adults, so it’s possible that slightly different dosages might be needed, for example. Of course, now that we know the vaccines are generally safe, there are a whole host of clinical trials either planned or under way to test the vaccines in children. In fact, the EU’s medicines agency, the EMA, seems to have made this a condition of authorising the various vaccines, that the companies selling them have a plan to carry out clinical trials in children. By the end of 2021, I expect that we will be starting to have results from these trials. As for pregnant women, this is always tricky because pregnant women rarely want to take part in clinical trials, for obvious reasons. Even though they tended to be specifically excluded from the clinical trials for Covid-19 vaccines, these trials take a long time, which means inevitably some women participated in these trials and then got pregnant after having had the jabs. None of them reported any specific problems, but there were very few, so we don’t know for sure. Here’s what the EMA says about the BioNTech/Pfizer vaccine and pregnant or breastfeeding women: “Preliminary animal studies do not show any harmful effects in pregnancy, however data on the use of Covid-19 Vaccine AstraZeneca during pregnancy are very limited. Although there are no studies on breast-feeding, no risk from breast-feeding is expected. The decision on whether to use the vaccine in pregnant women should be made in close consultation with a healthcare professional after considering the benefits and risks.” The EMA says the same thing about the Moderna and Oxford/AZ vaccines.

“Will this vaccine protect us against another coronavirus pandemic?”

Probably not. If (when) another coronavirus with pandemic potential comes up, it will almost certainly be quite different from SARS-CoV-2 in such a way that the current vaccines will not provide adequate protection against it. We already see differences in efficacy of vaccine protection between variants of SARS-CoV-2, which in the grand scheme of things are nearly identical to one another. It’s therefore very unlikely that these vaccines would be properly protective against a whole new coronavirus species. However, what is possible is that in the event of a new pandemic we could probably develop new vaccines against the new coronavirus more quicky than we have this time. It’s possible that we would only need to do phase 1 and 2 clinical trials, and if the results of these look very similar to the ones we did for SARS-CoV-2 with the current vaccines, then we might decide that the new vaccines are likely to be “equivalent” in terms of protection and so they might start being rolled out while we do the phase 3 studies. This would effectively save 6 months, and it’s similar to what we do at the moment with flu vaccines, which are different every year but don’t need to go through a full phase 3 trial before being rolled out.