Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study

Vikström, Linnea; Fjällström, Peter; Gwon, Yong-Dae; Sheward, Daniel J; Wigren-Byström, Julia; Evander, Magnus; Bladh, Oscar; Widerström, Micael; Molnar, Christian; Rasmussen, Gunlög; Bennet, Louise; Åberg, Mikael; Björk, Jonas; Tevell, Staffan; Thålin, Charlotte; Blom, Kim; Klingström, Jonas; Murrell, Ben; Ahlm, Clas; Normark, Johan; Johansson, Anders; Forsell, Mattias N.E.

doi:10.1016/j.lanepe.2023.100646

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…This agrees with earlier studies 10 and is important since it has been shown that binding antibodies, in the absence of neutralizing antibodies, are associated with protection from progression to severe disease. 17 We have also observed that individuals who have more extensive immune histories (previous infections plus vaccinations and individuals with 3 doses of vaccine) prior to breakthrough infection display lower induction of antibodies after BA.1 or BA.2 breakthrough. Two possible explanations could be that, first, their baseline antibody levels were already higher and therefore the calculated induction would be lower.…”

Section: Discussionmentioning

confidence: 62%

SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

Abbad,

Yellin,

Singh

et al. 2024

Cell Reports Medicine

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Section: Discussionmentioning

confidence: 62%

SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

Abbad,

Yellin,

Singh

et al. 2024

Cell Reports Medicine

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“…However, it has been reported that binding antibodies to spike protein are much better maintained against the variants as compared to neutralizing activity ( 5 ). These binding antibodies may—in addition to T-cell immunity—contribute to the mostly maintained protection from severe disease ( 6 ) as has been shown by a recent study ( 7 ).…”

Section: Introductionmentioning

confidence: 84%

“…Binding antibodies have been correlated with protection by Earle and colleagues early in the pandemic ( 14 ). Importantly, a recent study has shown that in the absence of robust neutralizing antibodies, binding antibodies are associated with protection from progression to severe COVID-19 and death ( 7 ). Nevertheless, at this point in time, it remains unclear if these cross-reactive binding antibodies do in fact provide a clinical benefit.…”

Section: Discussionmentioning

confidence: 99%

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The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all Orthocoronavirinae genera

Singh,

Abbad,

Kleiner

et al. 2024

mBio

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The Orthocoronavirinae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly cross-reactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, other betacoronaviruses including Middle Eastern respiratory syndrome coronavirus, and extending to alpha-, gamma-, and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these cross-reactive antibodies and their impact, there is the possibility that they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential. IMPORTANCE As demonstrated by severe acute respiratory syndrome coronavirus 2, coronaviruses pose a significant pandemic threat. Here, we show that coronavirus disease 2019 mRNA vaccination can induce significant levels of cross-reactive antibodies against diverse coronavirus spike proteins. While these antibodies are binding antibodies that likely have little neutralization capacity and while their contribution to cross-protection is unclear, it is possible that they may play a role in protection from progression to severe disease with novel coronaviruses.

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“…Several reports have highlighted that vaccination elicits a larger number of non-neutralizing antibodies than infection 15 , and that despite the well-documented loss of neutralizing activity against recently arisen variants of concern (VOCs), individuals vaccinated with the BNT162b2 and mRNA-1273 vaccines still exhibit protection from disease 16 . Of note, Earle and colleagues found that binding antibody titers alone correlate with protection 14 , and a more recent study showed that binding antibodies correlated with protection from progression to severe disease, even when neutralizing titers are significantly reduced 17 . Taken together, these data suggest that other factors aside from neutralization are important for the control and clearance of infection.…”

Section: Introductionmentioning

confidence: 99%

Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination

Clark,

Hoxie,

Adelsberg

et al. 2024

Preprint

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SummaryNeutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activityin vitrobut several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.

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Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study

Cited by 9 publications

References 30 publications

SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all Orthocoronavirinae genera

Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination

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