Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial

Kelly, Eimear; Greenland, Melanie; Whalley, Philip C.S. De; Aley, Parvinder K.; Plested, Emma; Singh, Nisha; Koleva, Stanislava; Tonner, Sharon; Macaulay, Grace; Read, Robert C.; Ramsay, Mary; Cameron, J. Claire; Turner, David P. J.; Heath, Paul T; Bernatoniene, Jolanta; Connor, Philip; Cathie, Katrina; Faust, Saul N; Banerjee, Indraneel; Cantrell, Liberty; Mujadidi, Yama F; Belhadef, Hanane Trari; Clutterbuck, Elizabeth A.; Anslow, Rachel; Valliji, Zara; James, Tim; Hallis, Bassam; Otter, Ashley; Lambe, Teresa; Nguyen‐Van‐Tam, Jonathan S; Minassian, Angela M.; Liu, Xinxue; Snape, Matthew D

doi:10.1016/j.jinf.2023.06.007

Cited by 5 publications

(4 citation statements)

References 23 publications

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“… 26 Another mRNA-based vaccine has also demonstrated antibody responses up to 9 months following completion of a two-injection primary series vaccination. 10 , 11 , 12 Our data also provide further evidence of the safety of mRNA-1273 in adolescents. One AE of chest pain was adjudicated as probable myocarditis; this event was mild and self-limited, with no evidence of sequelae, which is consistent with most cases of myocarditis post-vaccination.…”

Section: Discussionsupporting

confidence: 61%

See 1 more Smart Citation

Safety and durability of mRNA-1273–induced SARS-CoV-2 immune responses in adolescents: results from the phase 2/3 TeenCOVE trial

Figueroa,

Ali,

Berman

et al. 2024

eClinicalMedicine

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Section: Discussionsupporting

confidence: 61%

“… 9 However, longitudinal changes in immune response following vaccination in adolescents remain inadequately characterized. 10 , 11 , 12 …”

Section: Introductionmentioning

confidence: 99%

Safety and durability of mRNA-1273–induced SARS-CoV-2 immune responses in adolescents: results from the phase 2/3 TeenCOVE trial

Figueroa,

Ali,

Berman

et al. 2024

eClinicalMedicine

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“…As previously shown for young adolescents, vaccination with S-expressing RNA followed by a subsequent booster with the recombinant Novavax vaccine ( 59 ) led to fewer breakthrough infections and generated higher antibody and T-cell responses against wild-type and omicron variants than homologous mRNA vaccination ( 79 ). This implied that a heterologous mRNA/protein boost regimen is more efficient to induce humoral immune responses than the homologous mRNA/mRNA vaccine.…”

Section: Discussionmentioning

confidence: 86%

Heterologous DNA-prime/protein-boost immunization with a monomeric SARS-CoV-2 spike antigen redundantizes the trimeric receptor-binding domain structure to induce neutralizing antibodies in old mice

Pflumm,

Seidel,

Klein

et al. 2023

Front. Immunol.

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A multitude of alterations in the old immune system impair its functional integrity. Closely related, older individuals show, for example, a reduced responsiveness to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines. However, systematic strategies to specifically improve the efficacy of vaccines in the old are missing or limited to simple approaches like increasing the antigen concentration or injection frequencies. We here asked whether the intrinsic, trimeric structure of the SARS-CoV-2 spike (S) antigen and/or a DNA- or protein-based antigen delivery platform affects priming of functional antibody responses particularly in old mice. The used S-antigens were primarily defined by the presence/absence of the membrane-anchoring TM domain and the closely interlinked formation/non-formation of a trimeric structure of the receptor binding domain (S-RBD). Among others, we generated vectors expressing prefusion-stabilized, cell-associated (TM+) trimeric “S2-P” or secreted (TM−) monomeric “S6-PΔTM” antigens. These proteins were produced from vector-transfected HEK-293T cells under mild conditions by Strep-tag purification, revealing that cell-associated but not secreted S proteins tightly bound Hsp73 and Grp78 chaperones. We showed that both, TM-deficient S6-PΔTM and full-length S2-P antigens elicited very similar S-RBD-specific antibody titers and pseudovirus neutralization activities in young (2–3 months) mice through homologous DNA-prime/DNA-boost or protein-prime/protein-boost vaccination. The trimeric S2-P antigen induced high S-RBD-specific antibody responses in old (23-24 months) mice through DNA-prime/DNA-boost vaccination. Unexpectedly, the monomeric S6-PΔTM antigen induced very low S-RBD-specific antibody titers in old mice through homologous DNA-prime/DNA-boost or protein-prime/protein-boost vaccination. However, old mice efficiently elicited an S-RBD-specific antibody response after heterologous DNA-prime/protein-boost immunization with the S6-PΔTM antigen, and antibody titers even reached similar levels and neutralizing activities as in young mice and also cross-reacted with different S-variants of concern. The old immune system thus distinguished between trimeric and monomeric S protein conformations: it remained antigen responsive to the trimeric S2-P antigen, and a simple change in the vaccine delivery regimen was sufficient to unleash its reactivity to the monomeric S6-PΔTM antigen. This clearly shows that both the antigen structure and the delivery platform are crucial to efficiently prime humoral immune responses in old mice and might be relevant for designing “age-adapted” vaccine strategies.

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“…Researchers in the University of Oxford’s Com-COV3 study have reported that a dose of the Pfizer-BioNTech covid vaccine followed by a dose of the Novavax vaccine is more effective at protecting against infection and generates a higher antibody and T cell response in 12-16 year olds than a two dose Pfizer-BioNTech schedule. In their paper published in the Journal of Infection ,4 they said this was true of wild type SARS-CoV-2 and the BA.1/BA.2 omicron variants. No vaccine related safety concerns were raised in the study.…”

Section: Covid-19mentioning

confidence: 99%

Seven days in medicine: 5-11 July 2023

2023

BMJ

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Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial

Cited by 5 publications

References 23 publications

Safety and durability of mRNA-1273–induced SARS-CoV-2 immune responses in adolescents: results from the phase 2/3 TeenCOVE trial

Safety and durability of mRNA-1273–induced SARS-CoV-2 immune responses in adolescents: results from the phase 2/3 TeenCOVE trial

Heterologous DNA-prime/protein-boost immunization with a monomeric SARS-CoV-2 spike antigen redundantizes the trimeric receptor-binding domain structure to induce neutralizing antibodies in old mice

Seven days in medicine: 5-11 July 2023

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