Immunocompromise and durability of BNT162b2 vaccine against severe outcomes due to omicron and delta variants

Tartof, Sara Y; Slezak, Jeff; Puzniak, Laura; Hong, Vennis; Xie, Fagen; Ackerson, Bradley; Valluri, Srinivas Rao; Jódar, Luis; McLaughlin, John M.

doi:10.1016/s2213-2600(22)00170-9

Cited by 30 publications

(32 citation statements)

References 7 publications

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“…Notwithstanding the importance of vaccination with currently approved wild-type-strain based vaccines such as BNT162b2 that offer effective protection from severe disease by current VOCs including Omicron BA.1 and BA.2 ( 30, 31 ), our findings highlight that consideration of rapidly evolving epidemiological landscapes and newly emerging SARS-CoV-2 variants is of high importance for guiding vaccine adaptation programs. For instance, while the efficacy of vaccine adaptation to the BA.1 strain S glycoprotein sequence is currently under investigation in clinical trials, our data suggest that further benefit may be derived from a vaccine adapted to the sequence of BA.2 or descendants.…”

Section: Discussionmentioning

confidence: 93%

Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5

Muik¹,

Lui²,

Bacher³

et al. 2022

Preprint

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Recently, we reported that BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection have strong serum neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 variants of concern (VOCs), yet less against the highly contagious Omicron sublineages BA.4 and BA.5 that have displaced previous variants. As the latter sublineages are derived from Omicron BA.2, we characterized serum neutralizing activity of COVID-19 mRNA vaccine triple-immunized individuals who experienced BA.2 breakthrough infection. We demonstrate that sera of these individuals have broadly neutralizing activity against previous VOCs as well as all tested Omicron sublineages, including BA.2 derived variants BA.2.12.1, BA.4/BA.5. Furthermore, applying antibody depletion we showed that neutralization of BA.2 and BA.4/BA.5 sublineages by BA.2 convalescent sera is driven to a significant extent by antibodies targeting the N-terminal domain (NTD) of the spike glycoprotein, whereas their neutralization by Omicron BA.1 convalescent sera depends exclusively on antibodies targeting the receptor binding domain (RBD). These findings suggest that exposure to Omicron BA.2, in contrast to BA.1 spike glycoprotein, triggers significant NTD specific recall responses in vaccinated individuals and thereby enhances the neutralization of BA.4/BA.5 sublineages. Given the current epidemiology with a predominance of BA.2 derived sublineages like BA.4/BA.5 and rapidly ongoing evolution, these findings are of high relevance for the development of Omicron adapted vaccines.

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Section: Discussionmentioning

confidence: 93%

Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5

Muik¹,

Lui²,

Bacher³

et al. 2022

Preprint

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“…33,34 Thus, timing the administration of an annual COVID-19 vaccine, and thus peak vaccine protection, with the likely timing of peak COVID-19 disease activity (i.e., the winter viral respiratory season based on our results) may be the most prudent approach in the near term. Despite evidence that protection provided by current mRNA COVID-19 vaccines wanes significantly against omicron infection and symptomatic disease after only 3 to 4 months—even after a booster 4,7,35 —this short-term protection could still provide meaningful defense against SARS-CoV-2 infection if deployed just before seasonal waves that last 3 to 4 months on average. Moreover, it remains unknown whether variant-adapted vaccines may improve durability of protection against infection and symptomatic disease for even longer than current wild-type formulations.…”

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

“…Vaccination strategies to date have struggled to keep pace, and booster doses have been deployed to bolster protection against infection and symptomatic disease and maintain peak levels of protection against severe disease throughout the pandemic. [3][4][5][6][7] Nearly all respiratory viruses capable of causing human infection show distinct seasonal patterns and result in waves of illness during the winter months. 8,9 These patterns are likely caused by a combination of host, pathogen, and environmental factors, including increased indoor activity in the winter months and seasonal temperature and humidity fluctuations known to impact viral stability outside of the host.…”

Section: Introduction (2492 / 3000 Words)mentioning

confidence: 99%

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Is COVID-19 seasonal? A time series modeling approach

Wiemken

Khan

Nguyen

et al. 2022

Preprint

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Background Determining whether SARS-CoV-2 is or will be seasonal like other respiratory viruses is critical for public health planning, including informing vaccine policy regarding the optimal timing for deploying booster doses. To help answer this urgent public health question, we evaluated whether COVID-19 case rates in the United States and Europe followed a seasonal pattern using time series models. Methods We analyzed COVID-19 data from Our World in Data from Mar 2020 through Apr 2022 for the United States (and Census Region) and five European countries (Italy, France, Germany, Spain, and the United Kingdom). For each, anomalies were identified using Twitter's decomposition method and Generalized Extreme Studentized Deviate tests. We performed sensitivity analyses to determine the impact of data source (i.e., using US Centers for Disease Control and Prevention [CDC] data instead of OWID) and whether findings were similar after adjusting for multiple covariates. Finally, we determined whether our time series models accurately predicted seasonal influenza trends using US CDC FluView data. Results Anomaly plots detected COVID-19 rates that were higher than expected between November and March each year in the United States and Europe. In the US Southern Census Region, in addition to seasonal peaks in the fall/winter, a second peak in Aug/Sep 2021 was identified as anomalous. Results were robust to sensitivity analyses. Conclusions Our results support employing annual protective measures against SARS-CoV-2 such as administration of seasonal booster vaccines or other non-pharmaceutical interventions in a similar timeframe as those already in place for influenza prevention.

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“…Although we did not observe a significant relationship between increasing the proportion of fully vaccinated individuals and a reduction in COVID-19 cases, this was not completely unexpected. It has become clear that current (wild-type) COVID-19 vaccines cannot prevent all Omicron infections and that booster doses substantially improve neutralizing activity and protection against Omicron infection or symptomatic disease [ 4 , 6 , 15 , 16 ]. Thus, our findings reiterate the importance of booster doses in the context of Omicron.…”

Section: Discussionmentioning

confidence: 99%