SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses

Koutsakos, Marios; Reynaldi, Arnold; Lee, Wen Shi; Nguyen, Julie; Amarasena, Thakshila; Taiaroa, George; Kinsella, Paul; Liew, Kwee Chin; Tran, Thomas; Kent, Helen E; Tan, Hyon‐Xhi; Rowntree, Louise C.; Nguyen, Thi H. O.; Kedzierska, Katherine; Petersen, Jan; Rossjohn, Jamie; Williamson, Deborah A; Khoury, David S.; Davenport, Miles P.; Kent, Stephen J.; Wheatley, Adam K.; Juno, Jennifer A

doi:10.1016/j.immuni.2023.02.017

Cited by 67 publications

(43 citation statements)

References 52 publications

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“… 38 This observation suggests immunity uniquely elicited by infection augments protection against either acquiring re-infection, or alternatively developing symptoms during reinfection. While the greater magnitude and breadth of memory T cell responses seeded by prior infection likely act to limit disease severity, 45 it is also plausible that additional immune effectors at mucosal sites could directly limit acquisition. Two recent studies have suggested that concentrations of serum and mucosal sIgA were inversely associated with the risk of breakthrough infection, suggesting mucosal antibodies are actively contributing to barrier protection.…”

Section: Introductionmentioning

confidence: 99%

Mucosal vaccines for SARS-CoV-2: triumph of hope over experience

Pilapitiya¹,

Wheatley²,

Tan³

2023

eBioMedicine

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Section: Introductionmentioning

confidence: 99%

Mucosal vaccines for SARS-CoV-2: triumph of hope over experience

Pilapitiya¹,

Wheatley²,

Tan³

2023

eBioMedicine

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“…Given that prior COVID-19 infection could influence both systemic and more importantly, mucosal humoral responses following vaccination, we next wanted to explore how prior vaccination impacted systemic and mucosal humoral responses during COVID-19 breakthrough infections. To address this, we expanded our studies to breakthrough COVID-19 cohorts and collected serial saliva and plasma samples from vaccinated individuals with acute COVID-19 from two different VoC waves (Delta, Omicron BA.2) in Victoria, Australia (Figure 3a, Supp Figure 1b, c) [8, 13, 14]. SARS-CoV-2 viral load (nasal swabs) from both VoC waves had comparable viral loads as previously reported (Supp Figure 6a-b), which titered out by two weeks [8].…”

Section: Resultsmentioning

confidence: 99%

“…We also recruited previously vaccinated individuals with a nasal PCR-confirmed breakthrough COVID-19 [8, 13, 14] during the Delta and Omicron BA.2 waves in Victoria to provide serial blood and saliva samples (Supp Figure 1b, c).…”

Section: Methodsmentioning

confidence: 99%

Lasting first impression: Pre-existing immunity restricts mucosal antibody responses during Omicron breakthrough

Selva

Ramanathan

Haycroft

et al. 2023

Preprint

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Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from: COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19 recovered vaccinees (convalescent, vaccinated) and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19 recovered vaccinees displayed improved antibody neutralizing activity, FcγR engagement and IgA compared to COVID-19 uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2-specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma. IgG, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased pre-existing vaccine-induced immunity to the ancestral strain. Salivary antibodies delayed initiation of boosting following breakthrough COVID-19 infection, especially Omicron BA.2, however, rose rapidly thereafter. Our data highlight how pre-existing immunity shapes mucosal SARS-CoV-2-specific antibody responses and has implications for long-term protection from COVID-19.

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“…We will regularly encounter severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but there is uncertainty about the contribution that T cells make to clear the virus. Koutsakos et al 1 shed light on the response of memory T cells acquired from vaccination to a breakthrough infection. They demonstrate a direct correlation between the T cell response, their functionality and viral clearance.…”

mentioning

confidence: 99%

“…T cells recognize distinct viral epitopes of the Spike protein, which are less affected by mutations that characterize novel variants. 5 To address the contribution of T cells and antibodies in SARS-CoV-2 control after breakthrough infection (BTI), Koutsakos et al 1 conducted a longitudinal cohort study in 23 vaccinated individuals with a welldefined exposure history to the Delta, BA.1 and BA.2 variants of SARS-CoV-2. Nasal swabs and blood samples were collected frequently after infection to define in parallel viral quantity and SARS-CoV-2 specific responses.…”

mentioning

confidence: 99%