Could one dose of vaccine be sufficient? Some interesting new data

Media yesterday reported on research published last week in the New England Journal of Medicine. That study looked at the immune response to one versus two doses of vaccine and suggested that we might only need one dose to get immunity to the virus.  In this post I critically review these data and examine how they change what we currently know. 

Confusion alert!

This post is not about how long should the delay be between two doses, which has been the subject of much debate.  The question I address is will one dose of a new vaccine be sufficient?

What are the recent Johnson and Johnson (J&J) data?

• (You may also read stuff about this as a vaccine produced by Janssen: the latter is a Belgian- owned subsidiary of J&J)
• J&J have produced a vaccine very similar to the AstraZeneca vaccine: ie a harmless adenovirus onto which is bolted the genetic instructions to make the Covid-19 spike protein
• From the start of their clinical research programme, J&J have included a comparison of one dose versus two doses, which the other vaccine developers have not done
• Whether one dose will provide a sufficient level of protection for the public is being studied in a large-scale (Phase 3) trial comparing the numbers of cases of infection between the two groups – that is between one or two doses.
• Results from this trial may come out in the next two weeks
• On January 14th J&J provided the results from a small preliminary (Phase 1/2) study comparing the antibody response between one or two doses 

• These data are only from people aged under 55.  I understand the Phase 3 trial will include people aged up to 75
• They studied 2 dose levels of the vaccine: ‘high’ and ‘low’ (a bit like AstraZeneca, see below)
• They then compared people who had had one dose followed by a placebo  with those who had two doses of the active vaccine – for each of these two levels
• The results of the antibody response are shown below at 4 weeks after the second vaccine dose:

• To explain the labels in this chart: – as example ‘Low 1 dose’ means people in that group had two ‘jabs’: the first was the low dose of the active vaccine, the second was a placebo )
• The antibody units are a measure of how much antibody was produced, which in all 4 groups were almost zero before the first dose
• The graph clearly shows that there is a substantial increase in the level of antibodies from the zero baseline in all the four groups (from left to right)
  • 1^st jab low dose, 2^nd jab placebo
  • 1^st jab low dose, 2^nd jab low dose
  • 1^st jab high dose, 2^nd jab placebo
  • 1^st jab high dose, 2^nd jab high dose
• For the two groups whose second ‘jab’ contained just a placebo their levels of antibodies were not as high as the groups that had two jabs with the active vaccine.  
• The research then compared the antibody response at 8 weeks with that at 4 weeks and this is what they found:

• Firstly, and interestingly, the level of antibodies increased between 4 weeks versus 8 weeks after the first dose in the two groups that only had one ‘jab’ with the active vaccine,
• Secondly, (though as expected) the antibody levels were even  higher in people who had had two jabs with the active vaccine 
• I need to emphasise that:
  • These results are of antibody levels and may not be carried through into reduction in the number of infections 
  • The results are only from those aged under 55
• I thus await their the results of their much larger Phase 3  clinical trial with interest to answer the points above
• However these data raise the possibility that one dose of this vaccine may be sufficient to achieve herd immunity in the population more quickly

Recap about the data from AstraZeneca vaccine and one dose

• Given that the J&J vaccine is the same type as the AstraZeneca vaccine, how do the results on antibody response from the two vaccines compare? 
• Regular readers of this blog may recall that I presented this data in my post on 5^th January (see https://makingsenseofcovid19withs.com/2021/01/05/how-much-protection-is-there-after-one-dose-of-vaccine/)
• I am reproducing the AstraZeneca figure from that post  here as it is relevant in interpreting these new data from J&J
• AstraZeneca studied the level of immunity in people from 3 age groups, with two older age groups comprising half who had had one jab, and other half who had two jabs
• In this graph day ‘0 is the day of the first jab, day ’28’ is the day of the second jab (in those groups who had a second jab)

• After one dose of the AstraZeneca vaccine there were good levels of antibody response after 28 days*
• The antibody level in those two groups who just had one dose of vaccine (dotted lines) did then fall after 28 days, whilst for those who had a second dose of vaccine at 28 days, their antibody levels stayed high
• Thus despite the J&J and the AZ vaccines being of the same type, their results on the strength of the antibody response after one dose varied
• Although both vaccines give a good response after one dose but they were quite different in how long this is sustained

*we can’t compare the actual units between the AZ and J&J data because of differences in the way they measured antibody levels

Recap about about the data from Pfizer vaccine and one dose

• For completeness I will also recap about the data from one dose of the Pfizer vaccine 
• Pfizer only tested a two-dose regime, with the two doses 3 weeks apart
• They did, however, look separately at the number of cases of infection that developed in each of the two groups (active and placebo) in the interval between the first and second doses
• I have not shown you these data before, but they were used by the UK’s ‘Joint Committee on Vaccine and Immunization’  in deciding to accept that a longer delay between doses would still give worthwhile protection from the first dose
• I have now drawn a graph based on these data

• The two bars on the left show that there were about 50% fewer cases in the three-week period between doses in the active vaccine group (the first blue bar) than there were in the placebo group (the first orange bar)
• The numbers of cases in those 3 weeks were quite small so the infections rates may prove to be not very accurate
• The bars after two doses show what has already been widely publicised:  a 95% reduction in cases after two doses of active vaccine compared to two doses of placebo
• Given the design of the trial, we have no data on whether the 50% reduction in the number of cases after one dose would have persisted beyond the 3 weeks
• (At the risk of being repetitive!) at this moment we only know that one dose of the Pfizer vaccine gives some protection for at least 3 weeks.
• This may, and very well might, last the 12 week interval now operating between doses in the UK schedule but protection should not be assumed until after the second dose

Conclusion

• I hope I haven’t confused you more, but it was quite a challenge to interpret these data
• The first fact is that one dose of these 3 vaccines does produce a ‘good’ levels of antibodies
• Whether these levels  are ‘good enough’ is not known: there is likely to be a reduction in the number of people being ill but this will be less than that following two doses.  How much less and to what extent is an issue that remains to be determined
• There is also still another question mark:
  • We don’t know if the length of time any immunity lasts is meaningfully different following one or two doses of vaccine
• The only safe bet is that there will be further posts!

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