交差接種(ChAdOx1nCoV-19/BNT162b2)の免疫反応

//Special note//---
 Today, I have had a plan to share the contents of the other article. However, the important articles which needs to urgently communalize are published from Nature medicine and The New England Journal of Medicine. Therefore, I change the original plan. I introduce a part of contents about SARS-CoV-2 important reports exclusively today.
 
//Background//---
 SARS-CoV-2 pandemic is now ongoing. SARS-CoV-2 lineage continues to elevate social fitness through continuous mutation. Therefore, it is difficult for us to combat the pandemic socially, epidemiologically and medically. The key mutation for making social fitness of SARS-CoV-2 increase has two categories, one of which is to increase binding affinity like N501Y mutation, another of which is to escape immune response of antibody like E484K. On (a part of) B.1.1.7, B.1.351 and B.1.617 lineages, both key mutations are induced. Therefore, infection ability in the society is high, and efficacy of vaccine may partly decrease. Hence, the vaccine development and/or vaccination strategy to elevate fitness for any (emerging) mutations is highly demanded.
 Joana Barros-Martins, Swantje I. Hammerschmidt, Anne Cossmann et al. evaluate immune responses for heterologous ChAdOx1nCoV-19/BNT162b2 vaccination (Mixed dose) in an accelerated manner(1). I want to communalize a part of contents with the global important readers(1).
 
//Vaccine information//---
1: ChAdOx1nCoV-19 (AstraZeneca)
Non-replicative chimpanzee adeno-virus(Formation of S-protein) carrier vaccine
2: BNT162b2(Pfizer/BioNTech)
S-protein coded mRNA vaccine
 
//Condition//---
1: ChAdOx1nCoV-19 vaccination (Day 0)
1-1: ChAdOx1nCoV-19 booster vaccination (Day 73)
àAfter 16 days, plasma is analyzed in vitro.(n=32)
1-2: ChAdOx1nCoV-19/ BNT162b2 vaccination (Day 74)
àAfter 7 days, plasma is analyzed in vitro.(n=55)
Immune response of 1-1 Group and 1-2 Group is compared.
 
//Result(1)//---
(Antibody titer response through booster dose)
1-1(homologous): 2.9 fold increase
1-2(heterologous): 11.5 fold increase
---
(Neutralization ability against the key lineages: 50% inhibition)
*Wuhan wild type
1-1(homologous): 180-540 /1-2(heterologous): 540-1620
*B.1.1.7
1-1(homologous): 20-60 /1-2(heterologous): 180-540
*B.1.1.351
1-1(homologous): -20 /1-2(heterologous): 60-180
*P.1
1-1(homologous): -20 /1-2(heterologous):≒180
---
(IFN-gamma(type2) response)
 This interferon is associated with the response of cellular immunity (T cell, NK cell) and humoral immunity (B cell). Therefore, IFN-gamma partly play a role in the systemic immunity.
 1-2(heterologous) is higher than 1-1(homologous) for IFN-gamma response through boosting dose.
 
//Conclusion for result(1)//---
 The immune responses like antibody titer, neutralization ability and interferon-gamma become high in the heterologous vaccination compared to the homologous vaccination. However, as long as I evaluate, the ratio of (key mutant lineage)/(wildtype) is not drastically changed in the heterologous case, meaning the neutralization decreases alike.
 
//Discussion(1)//---
(Special note)
**The efficacy and safety of this protocol have not been sufficiently confirmed. However, the reactogenicity of heterologous vaccination has been investigate, resulting that systemic reactogenicity is tolerable compared to homologous vaccination(2). However, we need to carefully consider the application of heterogeneous vaccination in the current situation. On the other hand, this research paves the new way to combat future mutation risk.
---
*ChAdOx1nCoV-19 vaccination positive effect wasn’t confirmed for any symptom against the immune escape hallmarks B.1.351 linage(3)16. Therefore, in the current situation where the number of mRNA vaccine is lack for the global, heterogenous vaccine protocol needs to be considered even if interval for booster vaccination becomes long.
 
//Contributions//
Study design: G.M.N.B. and R.F. Data collection: J.B.-M., S.I.H., A.C., I.O., M.V.S., G.M.R., A.D.-J., A.H., C.R., M.F., C.S.-F., I.R., S.W., A.B., J.M., J.R., A.J., G.S., G.B., J.M., M.H., S.P. and T.K. Data analysis: J.B.-M., S.I.H., A.C., I.O., M.H., B.B. and M.V.S. Data interpretation: B.B., R.F. and G.M.N.B. Writing: B.B., G.M.N.B. and R.F., with comments from all authors.
 
(Reference)
(1)
Joana Barros-Martins, Swantje I. Hammerschmidt, Anne Cossmann, Ivan Odak, Metodi V. Stankov, Gema Morillas Ramos, Alexandra Dopfer-Jablonka, Annika Heidemann, Christiane Ritter, Michaela Friedrichsen, Christian Schultze-Florey, Inga Ravens, Stefanie Willenzon, Anja Bubke, Jasmin Ristenpart, Anika Janssen, George Ssebyatika, Günter Bernhardt, Jan Münch, Markus Hoffmann, Stefan Pöhlmann, Thomas Krey, Berislav Bošnjak, Reinhold Förster & Georg M. N. Behrens
Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination
Nature Medicine (2021)
---
Author information
Author notes
These authors contributed equally: Joana Barros-Martins, Swantje I. Hammerschmidt, Anne Cossmann.
Affiliations
Institute of Immunology, Hannover Medical School, Hannover, Germany
Joana Barros-Martins, Swantje I. Hammerschmidt, Ivan Odak, Christiane Ritter, Michaela Friedrichsen, Christian Schultze-Florey, Inga Ravens, Stefanie Willenzon, Anja Bubke, Jasmin Ristenpart, Anika Janssen, Günter Bernhardt, Berislav Bošnjak & Reinhold Förster
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
Anne Cossmann, Metodi V. Stankov, Gema Morillas Ramos, Alexandra Dopfer-Jablonka, Annika Heidemann & Georg M. N. Behrens
German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany
Alexandra Dopfer-Jablonka, Reinhold Förster & Georg M. N. Behrens
Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation, Hannover Medical School, Hannover, Germany
Christian Schultze-Florey
Institute of Biochemistry, University of Lübeck, Lübeck, Germany
George Ssebyatika & Thomas Krey
Ulm University Medical Center, Institute of Molecular Virology, Ulm, Germany
Jan Münch
Infection Biology Unit, German Primate Center, Göttingen, Germany
Markus Hoffmann & Stefan Pöhlmann
Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
Markus Hoffmann & Stefan Pöhlmann
German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig and Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
Thomas Krey
Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
Reinhold Förster
CiiM, Centre for Individualised Infection Medicine, Hannover, Germany
Georg M. N. Behrens
(2)
Shaw, R. H. et al.
Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data.
Lancet 397, 2043–2046 (2021).
(3)
Madhi, S. A. et al.
Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant.
N. Engl. J. Med. 384, 1885–1898 (2021).