Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

Background Heterologous prime-boost schedules with vector- and mRNA-based COVID-19 vaccines are already administered, but immunological responses and elicited protection have not been reported. Methods We here analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-2019 prime followed by a BNT162b2 boost after an 8-week interval for reactogenicity, antibody responses and T cell reactivity. Results Self-reported solicited symptoms after ChAdOx1 nCoV-2019 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers 2 weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 was 3.9-fold higher than in individuals receiving homologous BNT162b2 vaccination, only 2-fold reduced for variant of concern B.1.351, and similar for variant B.1.617. In addition, CD4+ and CD8+ T cells reacted to SARS-CoV-2 spike peptide stimulus 2 weeks after the full vaccination. Conclusions The heterologous ChAdOx1 nCoV-2019 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants of concern B.1.1.7, B.1.351 and B.1.617 are potently neutralized by sera of all participants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations.

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Protective Immunity to Nematode Infection Is Induced by CTLA-4 Blockade

Journal of Experimental Medicine ◽

10.1084/jem.186.2.183 ◽

1997 ◽

Vol 186 (2) ◽

pp. 183-187 ◽

Cited By ~ 83

Author(s):

Kathy McCoy ◽

Mali Camberis ◽

Graham Le Gros

Keyword(s):

T Cell ◽

Egg Production ◽

Recent Observation ◽

Acute Infection ◽

Neutralizing Antibody ◽

Cell Immune Response ◽

Nippostrongylus Brasiliensis ◽

Infectious Agents ◽

Cell Reactivity ◽

T Cell Reactivity

The recent observation that neutralization or genetic deletion of the T lymphocyte receptor CTLA-4 allows enhanced T cell reactivity offers new opportunities for immunotherapy against infectious agents. We used a neutralizing antibody to block CTLA-4 interaction with its ligands CD80 and CD86 during infection of mice with the nematode, Nippostrongylus brasiliensis. CTLA-4 blockade greatly enhanced and accelerated the T cell immune response to N. brasiliensis, resulting in a profound reduction in adult worm numbers and early termination of parasite egg production. The ability of CTLA-4 blockade to accelerate primary immune responses to a protective level during an acute infection indicates its potential as an immunotherapeutic tool for dealing with infectious agents.

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The MRC OX-22- CD4+ T cells that help B cells in secondary immune responses derive from naive precursors with the MRC OX-22+ CD4+ phenotype.

Journal of Experimental Medicine ◽

10.1084/jem.169.3.653 ◽

1989 ◽

Vol 169 (3) ◽

pp. 653-662 ◽

Cited By ~ 81

Author(s):

F Powrie ◽

D Mason

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Cd4 T Cells ◽

Antibody Responses ◽

Cell Reactivity ◽

Helper Activity ◽

T Cell Reactivity ◽

Paper Address

CD4+ T cells in the rat can be divided into two nonoverlapping subsets by their reactivity with the mAb MRC OX-22, which binds some of the high molecular weight forms of the CD45 antigen. The lineage relationship between subsets of CD4+ T cells expression different forms of CD45 has been a controversial issue for some time. Experiments described in this paper address this question using in vivo assays of T cell reactivity. Analysis of primary antibody responses in vivo show that it is MRC OX-22+ CD4+ T cells that are active in these assays, whereas antigen-primed T cells that provide helper activity for secondary antibody responses in vivo have the MRC OX-22- CD4+ phenotype. It is demonstrated that these memory T cells derive from MRC OX-22+ CD4+ T cell precursors and not from a putative separate lineage. It is concluded that with respect to the provision of help for B cells, MRC OX-22+ CD4+ T cells are precursors of memory cells with the phenotype MRC OX-22- CD4+.

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