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Vaccine combinations
Are their benefits in having mixtures of vaccines? eg first dose from AstraZeneca and second dose from Pfizer. This web page is a collection of articles on new (at 2/6/21) and evolving topic.
28/May/21 Anne de Gheest COVID Clinical update https://www.youtube.com/watch?v=8bI7V4lkKs4
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Europe is trialling this because of the high use of AstraZeneca in Europe.

Dr Norman Swan says over-50s should get AstraZeneca now + Pfizer booster at years end. Better protection than 2 Pfizer shots. 25/May/21
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At 2mins40 into this clip, Norman suggests that Aussie's 50+ will :
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be better off getting AstraZeneca now plus Pfizer booster at years end (He says that is what the Federal Government's policy SHOULD be promising to those Aussies 50+) THAN
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waiting for 2 shots of Pfizer at the end of the year. If you wait till year's end, you will be in the queue behind 12 years old, and you probably won't get Pfizer shot till well into 2022.
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Can I get AstraZeneca now and Pfizer later? 31/May/21
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In the face of changing eligibility for the AstraZeneca vaccine, new variants of the coronavirus and supply constraints, many people are wondering whether they can “mix and match” COVID-19 vaccines. This means, for example, having the AstraZeneca vaccine as the first dose, followed by a different vaccine such as Pfizer as the second dose, and boosters with other vaccines later on.
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While many studies are ongoing, data has recently been released from mix and match trials in Spain and the United Kingdom. This data is very promising, and suggests mix and match schedules may give higher antibody levels than two doses of a single vaccine.
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Heterologous prime-boost COVID-19 vaccination. UK. 12/May/21
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Com-COV (ISRCTN 69254139) is a UK multi-centre, participant-masked, randomised heterologous prime-boost COVID-19 vaccination study comparing all four prime-boost permutations of the ChAd (AstraZeneca) and BNT (Ppfizer) vaccines both at 28-day and 84-day prime-boost intervals.
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The Carlos III Health Institute (ISCIII) presented on Tuesday the preliminary results of the CombivacS clinical trial , which is evaluating the response of the immune system (immunogenicity) and the safety associated with the use of a heterologous vaccination regimen (combination of different vaccines) against the SARS-CoV-2 coronavirus. The CombivacS study is the first worldwide to provide data on immunogenicity derived from the combined use of two different vaccines; It is a phase 2 clinical trial,.... in which the administration of the Comirnaty vaccine against the SARS-CoV-2 coronavirus (BioNtech / Pfizer) has been analyzed in people under 60 years who had already received a first and only dose of Vaxzevria ( AstraZéneca ); the participants had to be at least in the eighth week post-first dose.
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The first results indicate that this heterologous vaccination regimen is highly immunogenic and does not present problems of post-vaccination reactogenicity different from those already reported in the homologous use (alone) of these same vaccines; that is, the response of the immune system is greatly enhanced after the second dose of the Comirnaty (Pfizer) vaccine
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Different European countries, including Germany, France, Sweden, Norway and Denmark, are already recommending combined vaccination regimens in people under 60 years of age who have received a first dose of Vaxzevria(AstraZéneca)
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What’s the benefit of mixing and matching?
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If one vaccine is less effective than another against a certain variant, mix and match schedules could ensure people who’ve already received one dose of a vaccine with lower effectiveness could get a booster with a vaccine that’s more effective against the variant.
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Several countries in Europe are now advising younger people previously given this vaccine as a first dose should receive an alternative vaccine as their second dose, most commonly mRNA vaccines such as Pfizer’s.
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Mix-and-match COVID vaccines trigger potent immune response 19/May/21 Nature magazine.
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Preliminary results from a trial of more than 600 people are the first to show the benefits of combining different vaccines.
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Preliminary results from the trial of more than 600 people — announced in an online presentation on 18 May — are the first to show the benefits of combining different coronavirus vaccines. A UK trial of a similar strategy reported safety data last week, and is expected to deliver further findings on immune responses soon.
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Because of safety concerns, several European countries are already recommending that some or all people who were given a first dose of the vaccine developed by the University of Oxford, UK, and AstraZeneca in Cambridge, UK, get another vaccine for their second dose.
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“It appears that the Pfizer vaccine boosted antibody responses remarkably in one-dose AstraZeneca vaccinees. This is all around wonderful news,” says Zhou Xing, an immunologist at McMaster University in Hamilton, Canada.
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That is what researchers hoped for and expected from mixing different vaccines, a strategy known as a heterologous prime and boost, which has been deployed for vaccines against other diseases, such as Ebola. “These responses look promising and show the potential of heterologous prime–boost regimens,” says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, Massachusetts.
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Xing says the antibody response to the Pfizer boost seems to be even stronger than the one most people generate after receiving two doses of the Oxford–AstraZeneca vaccine, according to earlier trial data. But it is not clear how those responses compare with those seen in people who receive two doses of mRNA vaccines such as Pfizer–BioNTech’s, which tend to trigger an especially potent antibody response after a second dose.
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COVID vaccine Australia: New hope that mixing vaccines might provide a bonus (afr.com) 26/May/21
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Combination schedules might be even smarter than we think, he (Professor Nolan, head of the Vaccine and Immunisation Research Group at Melbourne’s Doherty Institute) said. “There’s a prospect that mixing two vaccines aimed at the original Wuhan strain might provide an immune response sufficiently elevated to give greater protection against the South African, UK and Indian strains. “Were this to happen, it would be a big bonus because it would remove the need for a third booster against variants.
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There is also the prospect of three doses. It could be that a third dose of the same vaccine prolongs the protection afforded by the first two and broadens the response to new variants because the person has so many more antibodies.
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The Oxford group is evaluating this in a three-dose trial using AstraZeneca and Pfizer to measure the antibody response generated. It is funded by the British government, which does not want to risk locking down for another winter. There is also the prospect of two AstraZeneca shots followed by a Pfizer booster, or vice versa. Moderna is yet another option. Australia has two lots of Moderna on order, with the batches due in 2022 expected to be tweaked to for new variants.
Canada allows AstraZeneca vaccine recipients to get Pfizer or Moderna jab for second dose 2/Jun/1
https://twitter.com/EricTopol/status/1408556241559842816 26/June/21
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Just published @TheLancet Largest mix-and-match, randomized, clinical vaccine trial of people with AZ first dose, Pfizer 2nd dose. Safe and notable improved neutralizing antibody and T cell response with mix vs controls (no 2nd dose)
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https://twitter.com/EricTopol/status/1408590002146004993 26/June/21
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"In conclusion, heterologous [fancy medical word for mix-and-match here] vaccination regimens against COVID-19 provide an opportunity to speed up vaccination campaigns worldwide, maximising their impact on the control of the pandemic."
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https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01442-2/fulltext
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The rapid development of vaccines against COVID-19 is the biggest achievement of science in the fight against the pandemic. ....
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Safety concerns regarding the ChAdOx1-S (AstraZeneca/Oxford University) vaccine have led some European countries (eg, Denmark) to minimise its use, with other countries recommending the switch from the trial-tested homologous booster to a heterologous booster, such as with BNT162b2 (Pfizer/BioNTech vaccine).
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https://science.sciencemag.org/content/372/6549/1392 "Hybrid Immunity" 25/June/21
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But the adaptive immune system is complex, and these factors may differ between natural immunity (obtained by infection) and vaccine-generated immunity (1). Additionally, there is the question of the combination: What kind of immunity develops in people with natural immunity who are subsequently vaccinated? Such “hybrid immunity” is particularly interesting because of the notable finding that people with previous SARS-CoV-2 infection mount unusually potent immune responses to COVID-19 vaccines. The following slide comes from Anne de Gheest's latest COVID clinical update (that came out yesterday) https://www.youtube.com/watch?v=77skcFyRWXE

Germany recommends mRNA Covid vaccine after AstraZeneca 1/July/2021
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Germany's Standing Vaccine Commission (STIKO) has issued updated Covid vaccination advice in light of the spread of Delta, stating that the second dose after AstraZeneca should be an mRNA vaccine, regardless of the patient's age.
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Under the latest advice, people who have received a first dose of AstraZeneca should in future receive an mRNA vaccine such as BioNTech or Moderna as their second injection, regardless of their age, the committee announced on Thursday.
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The interval between the first and second dose should then be at least four weeks. The recommendation will apply “subject to the feedback from the comment procedure,” it said.
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The advice is justified by recent studies that have shown that the immune response after two doses of different types of vaccine – first vector, then mRNA vaccine – is “clearly superior” to the immune response after two doses of AstraZeneca.