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1.
mBio ; : e0222322, 2022.
Article in English | MEDLINE | ID: covidwho-2038242

ABSTRACT

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates that the global scientific community monitor, assess, and respond to the evolving coronavirus disease (COVID-19) pandemic. But the current reactive approach to emerging variants is ill-suited to address the quickly evolving and ever-changing pandemic. To tackle this challenge, investments in pathogen surveillance, systematic variant characterization, and data infrastructure and sharing across public and private sectors will be critical for planning proactive responses to emerging variants. Additionally, an emphasis on incorporating real-time variant identification in point-of-care diagnostics can help inform patient treatment. Active approaches to understand and identify "immunity gaps" can inform design of future vaccines, therapeutics, and diagnostics that will be more resistant to novel variants. Approaches where the scientific community actively plans for and anticipates changes to infectious diseases will result in a more resilient system, capable of adapting to evolving pathogens quickly and effectively.

2.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-330496

ABSTRACT

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors, and are cross-reactive against diverse SARS-CoV-2 variants, including the extremely neutralization resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.

3.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327015

ABSTRACT

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

4.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326997

ABSTRACT

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, crossrecognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

6.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296585

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections. Highlights: A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotypeSerological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunityEvolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination. Graphical abstract:

7.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296584

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only or vaccinated and previously infected. We also investigated whether the virus still requires binding to the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa. We then compared neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation. Neutralization was by blood plasma from South African BNT162b2 vaccinated individuals. We observed that Omicron still required the ACE2 receptor to infect but had extensive escape of Pfizer elicited neutralization. However, 5 out of 6 of the previously infected, Pfizer vaccinated individuals, all of them with high neutralization of D614G virus, showed residual neutralization at levels expected to confer protection from infection and severe disease (2). While vaccine effectiveness against Omicron is still to be determined, these data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly by boosting, could maintain reasonable effectiveness against Omicron. If neutralization capacity is lower or wanes with time, protection against infection is likely to be low. However, protection against severe disease, requiring lower neutralization levels and involving T cell immunity, would likely be maintained.

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