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How much protection is there after one dose of vaccine?

Pfizer/BioNtech together with the US and European regulators have criticised the UK authorities for allowing up to 12 weeks between vaccine doses, news which was headlines in Australia today.

The UK now recommends a 3 month gap between doses of the Pfizer vaccine which  coincided with the UK regulator also recommending a 3 month gap between doses for the AstraZeneca vaccine.  

Public Health Argument

As is now well known worldwide, the UK is the epicentre of a major uncontrolled epidemic of new variant Covid-19.  As mentioned in the UK Prime Minister’s press briefing this afternoon, the UK government, aware of constraints in the availability of vaccine and the logistics for widespread delivery, is focusing on maximising the number of people to get their first dose, and delaying the second dose for 3 months for both of these 2 vaccines.

  • Support for this comes from a re-analysis of the AstraZeneca trial, which showed a greater protection against infection the longer the interval between vaccine doses from 28 up to 84 days.
  • The UK’s argument for the dose delay for the Pfizer vaccine  is that it is also likely that even with a 3 month interval between doses there should not be any reduction in the benefit achieved
  • Thus,  given the urgent public health need, it is better to direct resources to give as many people as possible one dose in the hope they would get some level of protection 

What this post adds to the debate?

In this post I review some of the laboratory data on the vaccines from last summer but also some very recent data from AstraZeneca that was published in December.  I use this new information to address again:

  • What protection can there be from just one dose?
  • How long would such protection last if there was not a second dose?

I have looked at the data from the Pfizer/BioNtech, Oxford AstraZeneca and Moderna/NIAID* vaccines to address these questions

*US National Institute of Allergic and Infectious Diseases.

The pyramid approach to assessing the value of vaccines 

  • Developing and testing vaccines is a costly and lengthy business
  • Following toxicity testing in animals and  healthy human volunteers, a vaccine’s effectiveness is assessed by a series of research steps
  • First research question – the yellow slice: does the body make antibodies* and how much?

*There is another part of the immune system-‘T cells’ which is part of our response to vaccines, but is not discussed here

  • The next research question: the grey slice: having made these antibodies, do they do anything useful for fighting infection, such as stopping the virus multiplying? We use the term ‘neutralising’ – it has a military tone as in neutralising the enemy!
  • All the 3 vaccines showed they could produce ‘neutralising’ antibodies
  • The third major research question – the orange slice: do these antibodies actually stop the occurrence of clinical cases of infection?
  • To address this, phase 3’ studies of all 3 vaccines recruited large numbers of volunteers who entered randomised trials
  • It was the success of these ‘phase 3’ studies at the end of last year that has led to the starting of the worldwide vaccination programme

Phase 3 studies did not look at the protection after just one dose!

  • At the moment we really have no data from these phase 3 studies to answer the question: “will one dose provide sufficient protection against infection?”
  • The reason is a simple one which is that the phase 3 studies for all these 3 vaccines only looked at a vaccination regime that required 2 vaccine doses and, further, the trials only started counting the people who had developed an infection after the second dose.  
  • The actual numbers in each trial that were published are shown below
  • The AstraZeneca trial, with their wider gap could have looked at the number of cases between doses but their protocol was only designed to test the efficacy of a two dose regime
  • Thus in the AstraZeneca data available to me, I cannot find any analysis of protection that may have occurred in the interval between the doses
  • Thus, none of the major trials that collected data can answer the question on how far any of the vaccines can prevent new cases with just one dose
  • This does not mean that one dose cannot prevent cases occurring we just do not know how large this reduction might be

Note to readers, you might just want to go to my conclusions at the end of this post-that’s fine: I use the detailed dissection of the antibody data below to justify these conclusions

Thus, the basis why those advising the UK government and others believe that there may be a reasonable level of protection after the first dose is likely to be based just on the laboratory antibody, and especially the neutralising antibody, data (the ‘yellow and grey slices’ of my pyramid).  These data are discussed below.

Antibody levels after one and two doses of the AstraZeneca Vaccine

  • Last summer AstraZeneca recruited
    • 100 people aged 18-55
    • 120 people aged 56-69
    • 200 people aged over 70
  • The volunteers in the two older age groups were then divided into two groups: half who received just one dose of the vaccine and half who received two doses.
  • In this study all those who received a second dose did this after a 28 day interval
  • Antibody levels were measured in everyone after 28, 42 and 56 days (4, 6 and 8 weeks)
  • This is what they found:
  • The amount of antibody response is shown on the vertical axis (on a log scale)
  • The first and important finding is that antibody levels rose rapidly by 28 days in people in all 3 age groups 
  • In the two older groups, who only had one dose of vaccine, (the orange and purple dashed lines), the antibody levels broadly remained level  over the next 28 days
  • In all age groups that had two doses of vaccine, the levels of antibody continued to rise to reach a peak after 42 days and levelled off after
  • As mentioned above antibodies themselves may not be protective and in a separate analysis the levels of neutralising antibodies were examined and this is what they found (same key for age group): 
  • In this case again, there was a rise in neutralising antibodies after the first dose in all age groups. 
  • In those who only had one dose of the vaccine (the dashed lines again) the levels did fall between 28 and 56 days
  • In those who had a second dose the levels rose to a peak by 42 days and then had  dropped slowly by 56 days
  • To repeat, we do not know though from this type of research at what level of neutralising antibody is needed to protect against infection

Antibody protection after one dose of Pfizer and Moderna Vaccines

  • I just provide the brief summary of my findings from two articles in the prestigious new England Journal or Medicine
  • The Pfizer study focused on looking at the immune response after two doses of vaccine 21 days apart
    • In that study the maximal level of neutralising antibody levels were found 2 weeks after the second dose of the vaccine
    • In their study levels of neutralising antibodies were low after 21 days before the second dose was administered
  • This Moderna vaccine study examined the  antibody response in volunteers who had two vaccine doses 28 days apart
    • The Moderna vaccine is the identical type (RNA) to the Pfizer vaccine 
    • In this  study neutralising antibodies were much higher after the second dose which the authors argue “support the need for a two-dose schedule”

Conclusions

  • No authority in the West is  suggesting that any of the vaccines should be given as a single dose, the issue is what is the protection in the time between doses 
  • All the 3 vaccines now licensed in Western countries will produce some protective neutralising antibodies after one dose
  • The level of neutralising antibodies though is greater after two doses, and without a second dose may wane
  • In my previous post on the AstraZeneca vaccine* I had shown that a gap of 12 weeks may be optimal to achieve maximal clinical benefit.  
  • These new data do not contradict that observation as the second dose after a long gap of 12 weeks may tickle up the immune system more efficiently
  • What remains unknown is whether whilst waiting for a second dose for any of the vaccines there is sufficient protection from a single dose
  • Given that, I would happily accept an offer to have my first dose of any of the vaccines tomorrow, but I would consider myself unprotected until I had the second dose

*https://makingsenseofcovid19withs.com/2020/12/30/vaccines-1-or-2-doses-and-how-far-apart/

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7 replies on “How much protection is there after one dose of vaccine?”

This is very helpful and is on a higher plane altogether than most coverage that lay people can receive on the virus. Thank you so much for all your postings.

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Informative post as ever and totally agree with the last point in your conclusion as believe we would all need to be careful and shouldn’t consider ourselves protected until we had the second dose

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Thankyou for that analysis Alan. I’m concerned that with Johnson saying that a certain number of people have been ‘vaccinated’ rather than ‘fully vaccinated’ ( or some similar terminology) people will stip being cautious sooner than they should. Also I have seen some suggest that changing the regime from that devised by the manufaturers could risk the development of more mutations ( perhaps as taking half a dose of antibiotics risks antibiotic resitant strains of bacteria) Do you think this is a risk?

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Very good point about ‘fully vaccinated’, but that is politicians. No-one can be sure about mutations and vaccine effectiveness. It could well be a worry if people got infected when they were inadequately vaccinated. Though the experience from the AZ trial was that the increase in interval was helpful in terms of increasing protection – of course counting cases after the second dose

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