SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies

Jeffery-Smith, Anna; Burton, Alice R.; Lens, Sabela; Rees-Spear, Chloe; Davies, J. W.; Patel, Monika; Gopal, Robin; Muir, Luke; Aiano, Felicity; Doores, Katie J.; Chow, Ji‐Jian; Ladhani, Shamez; Zambon, Maria; McCoy, Laura E; Maini, Mala K.

doi:10.1172/jci152042

Cited by 31 publications

(33 citation statements)

References 69 publications

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“…Memory B cell recall occurs in the vast majority of SARS-CoV-2 vaccinated and convalescent individuals [ 37 , 38 , 39 , 40 ]. While the waning of antibody levels is natural due to the short half-life of antibodies [ 27 , 28 ], concerns were raised about what happens to a very specific subset of participants who had a blunted serological response demonstrated by significantly lower initial antibody concentrations after vaccination (* p = 0.026; mean for cohort = 44.8 µg/mL, mean for subset = 11.77 µg/mL).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Waning on Antibody Levels and Memory B Cell Recall following SARS-CoV-2 Infection or Vaccination

et al. 2022

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In order to longitudinally track SARS-CoV-2 antibody levels after vaccination or infection, we assessed anti-RBD antibody levels in over 1000 people and found no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, a significant waning of antibody levels was observed following vaccination. Participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to higher antibody levels, which were maintained at higher levels than in previously infected, unvaccinated participants. Older participants exhibited lower level of antibodies after vaccination, but a higher level after infection than younger people. The rate of antibody waning was not affected by pre-immunity or age. Participants who received a third dose of an mRNA vaccine not only increased their antibody levels ~14-fold, but also had ~3 times more antibodies compared to when they received their primary vaccine series. PBMC-derived memory B cells from 13 participants who lost all circulating antibodies were differentiated into antibody secreting cells (ASCs). There was a significant recall of memory B cell ASCs in the absence of serum antibodies in 5–8 of the 10 vaccinated participants, but not in any of the 3 infected participants, suggesting a strong connection between antibody levels and the effectiveness of memory B cell recall.

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Section: Discussionmentioning

confidence: 99%

The Effect of Waning on Antibody Levels and Memory B Cell Recall following SARS-CoV-2 Infection or Vaccination

et al. 2022

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“…Memory B cell recall occurs in the vast majority of SARS-CoV-2 vaccinated and convalescent individuals [30][31][32][33] . While the waning of antibody levels is natural due to the short halflife of antibodies 22,23 , concerns were raised about what happens to a very specific subset of participants who had a blunted serological response demonstrated by significantly lower initial antibody concentrations after vaccination (*p=0.026; mean for cohort = 44.8 µg/mL, mean for subset = 11.77 µg/mL).…”

Section: Discussionmentioning

confidence: 99%

The effect of waning on antibody levels and memory B cell recall following SARS-CoV-2 infection or vaccination

Forgacs

Silva-Moraes

Hanley

et al. 2022

Preprint

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As of March 2022, there have been over 450 million reported SARS-CoV-2 cases worldwide, and more than 4 billion people have received their primary series of a COVID-19 vaccine. In order to longitudinally track SARS-CoV-2 antibody levels in people after vaccination or infection, a large-scale COVID-19 sero-surveillance progam entitled SPARTA (SeroPrevalence and Respiratory Tract Assessment) was established early in the pandemic. Anti-RBD antibody levels were tracked in more than 1,000 people. There was no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, significant waning of antibody levels was observed following vaccination, regardless of previous infection status. Moreover, participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to significantly higher antibody levels, and antibodies were maintained at significantly higher levels than in previously infected, unvaccinated participants. This pattern was entirely due to differences in the magnitude of the initial seroconversion event, and the rate of antibody waning was not significantly different based on the pre-immune status. Participants who received a third (booster) dose of an mRNA vaccine not only increased their anti-RBD antibody levels ~14-fold, but they also had ~3 times more anti-RBD antibodies compared to the peak of their antibody levels after receiving their primary vaccine series. In order to ascertain whether the presence of serum antibodies is important for long-term seroprotection, PBMCs from 13 participants who lost all detectable circulating antibodies after vaccination or infection were differentiated into memory cells in vitro. There was a significant recall of memory B cells in the absence of serum antibodies in 70% of the vaccinated participants, but not in any of the infected participants. Therefore, there is a strong connection between anti-RBD antibody levels and the effectiveness of memory B cell recall.

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“…SARS-CoV-2 binding and neutralizing antibodies show measurable waning post-infection [ 226 , 234 , 235 ], which may correlate with risk of breakthrough infection [ 236 ]. However, memory B cells can persist after SARS-CoV-2 infection and vaccination [ 226 , 237 ] even after neutralizing antibodies become undetectable in the blood [ 238 ].…”

Section: How ‘Specific’ Is Sars-cov-2-specific Immunitymentioning

confidence: 99%

The past, current and future epidemiological dynamic of SARS-CoV-2

Balloux

Tan

Swadling

et al. 2022

Oxford Open Immunology

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SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 in China, and rapidly spread throughout the world to reach all continents. As the virus expanded in its novel human host, viral lineages diversified through the accumulation of around two mutations a month on average. Different viral lineages have replaced each other since the start of the pandemic, with the most successful Alpha, Delta and Omicron Variants of Concern (VoCs) sequentially sweeping through the world to reach high global prevalence. Neither Alpha nor Delta was characterised by strong immune escape, with their success coming mainly from their higher transmissibility. Omicron is far more prone to immune evasion and spread primarily due to its increased ability to (re-)infect hosts with prior immunity. As host immunity reaches high levels globally through vaccination and prior infection, the epidemic is expected to transition from a pandemic regime to an endemic one where seasonality and waning host immunisation are anticipated to become the primary forces shaping future SARS-CoV-2 lineage dynamics. In this review, we consider a body of evidence on the origins, host tropism, epidemiology, genomic and immunogenetic evolution of SARS-CoV-2 including an assessment of other coronaviruses infecting humans. Considering what is known so far, we conclude by delineating scenarios for the future dynamic of SARS-CoV-2, ranging from the good—circulation of a fifth endemic ‘common cold’ coronavirus of potentially low virulence, the bad—a situation roughly comparable to seasonal flu, and the ugly—extensive diversification into serotypes with long-term high-level endemicity. Lay Summary SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 and spread globally causing the COVID-19 pandemic. When SARS-CoV-2 jumped into humans, it had essentially no genetic diversity, but as the viral population expanded, it diversified into myriad genetically distinct lineages through the acumulation of approximately two mutations a month. The vast majority of those lineages are now extinct. The most successful lineages so far were the Alpha, Delta and Omicron variants which all reached global prevalence and replaced each other in the process. Alpha and Delta emerged in late 2020 and spread at a time when immunisation of the human population was still low and reached global prevalence primarily by being more transmissible. Omicron started expanding in late 2021, at a time when a large proportion of the human population had already been vaccinated and/or exposed to SARS-CoV-2. Omicron was so successful mainly due to its ability to (re-)infect hosts with prior immunity. In this review, we provide an overview of the evolution of SARS-CoV-2 and put it in context of what is known about other coronaviruses infecting humans. We conclude by delineating plausible scenarios for the ‘endemic’ future of SARS-CoV-2.

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SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies

Cited by 31 publications

References 69 publications

The Effect of Waning on Antibody Levels and Memory B Cell Recall following SARS-CoV-2 Infection or Vaccination

The Effect of Waning on Antibody Levels and Memory B Cell Recall following SARS-CoV-2 Infection or Vaccination

The effect of waning on antibody levels and memory B cell recall following SARS-CoV-2 infection or vaccination

The past, current and future epidemiological dynamic of SARS-CoV-2

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