COVID-19: XBB.1.5 escapes neutralizing antibody (NAb) responses after bivalent mRNA boosting

0
272

An independent study conducted by researchers from Beth Israel Deaconess Medical Center, Boston-USA and also the Los Alamos National Laboratory, New Mexico-USA has found that the XBB.1.5 variant escapes neutralizing antibody responses after bivalent mRNA boosting, raising questions about the efficacy of the bivalent shots.

The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2023.01.22.525079v1

The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England.

The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined.

We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting.

Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape.

By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.

The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations (Fig. 1A). XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England (Fig. S1).

The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants1-4, but the durability of these responses remains to be determined.

We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting (Table S1). By month 3, 43% of participants had a known COVID-19 infection, although we speculate that this represents an underestimate of the true rate of infection.

At baseline, median NAb titers to WA1/2020, BA.2, BA.5, BQ.1.1, XBB.1, and XBB.1.5 were 5015, 118, 104, 59, 46, and 74, respectively, in nucleocapsid seronegative participants (Fig. 1B). At week 3, median NAb titers to WA1/2020, BA.2, BA.5, BQ.1.1, XBB.1, and XBB.1.5 were 25,954, 5318, 2285, 379, 125, and 137, respectively (Fig. 1B). At month 3, median NAb titers to WA1/2020, BA.2, BA.5, BQ.1.1, XBB.1, and XBB.1.5 were 21,804, 3996, 1241, 142, 59, and 76, reflecting 1.2-, 1.3-, 1.8-, 2.7-, 2.1-, and 1.8-fold declines from week 3, respectively (Fig. 1B).

Spike-specific T cell responses were assessed by intracellular cytokine staining assays. Median CD4+ T cell responses to WA1/2020, BQ.1.1, and XBB.1.5 were 0.098%, 0.072%, and 0.065% at baseline and 0.099%, 0.073%, and 0.090% at month 3, respectively (Fig. 1C). Median CD8+ T cell responses to WA1/2020, BQ.1.1, and XBB.1.5 were 0.080%, 0.060%, and 0.059% at baseline and 0.107%, 0.125%, and 0.106% at month 3, respectively (Fig. 1C).

Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape.

By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly. The combination of low magnitude and rapidly waning NAb titers to XBB.1.5 will likely reduce the efficacy of the bivalent mRNA boosters5, but cross-reactive T cell responses, which were present prior to boosting, may continue to provide protection against severe disease.

The recently detected XBB.1.5 variant is a sub-lineage of the Omicron XBB sub-lineage. Although data on XBB.1.5 are still very limited, currently available information indicates that XBB.1.5 has a growth advantage compared to other circulating Omicron sublineages and may therefore contribute to an increase in cases globally.

Additionally, as per preliminary laboratory-based studies, this sublineage evades antibodies in humans at equal rate as o XBB* variants are the most antibody-resistant variants to date. No data are currently available regarding the severity of disease associated with XXB.1.5 but assessments are ongoing.  

Between 22 October 2022 and 11 January 2023, 5288 sequences of XBB.1.5 have been reported from 38 countries. The majority of these sequences are from the United States of America (82.2%), United Kingdom of Great Britain and Northern Ireland (8.1%), and Denmark (2.2%). Our understanding of the transmissibility, immune escape and severity of disease will increase as more data become available from additional countries. To date, 2 countries in the Eastern Mediterranean Region have reported Omicron subvariant XBB.1.5  

WHO’s Technical Advisory Group on Virus Evolution (TAG-VE) met on 5 January 2023 to discuss the latest evidence on XBB.1.5 and review the public health risks associated with this variant. As part of its recommendations, TAG-VE urged Member States to expand sequencing and reinforce surveillance to detect and track the emergence and spread of SARS-CoV-2 new variants, such as XBB.1.5. This will significantly allow well-informed conclusions about their transmissibility, immune escape, severity, and impact on response interventions such as diagnostics, therapeutics and vaccines. 

Updates in WHO mask use recommendations 

On 13 January 2023, WHO updated its guidelines on mask wearing in community settings, COVID-19 treatments, and clinical management. WHO continues to recommend the use of masks by the public in specific situations, regardless of the local epidemiological situation, given the current spread of the COVID-19 globally. Previously, WHO recommendations were based on the epidemiological situation. Masks are recommended following recent exposure to COVID-19, when someone has or suspects they have COVID-19, when someone is at high-risk of severe COVID-19, and for anyone in a crowded, enclosed, or poorly ventilated space.  

Updates in isolation period for COVID-19 patients 

For patients with symptoms, the new guidelines suggest 10 days of isolation from the date of symptom onset. Previously, WHO advised that patients be discharged 10 days after symptom onset, plus at least 3 additional days since their symptoms had resolved.

For those who test positive for COVID-19 but do not have any signs or symptoms, WHO now suggests 5 days of isolation, compared to 10 days previously.

The patient can be discharged from isolation early if they test negative on an antigen-based rapid test.

Isolation of people with COVID-19 is an important step in preventing others from being infected. This can be done at home or at a dedicated facility, such as a hospital or clinic.

The evidence considered by the guideline development group showed that people without symptoms are much less likely to transmit the virus than those with symptoms. Although of very low certainty, evidence also showed that people discharged at day 5 following symptom onset risked infecting 3 times more people than those discharged at day 10.

Review of COVID-19 treatments 

WHO has extended its strong recommendation for the use of nirmatrelvir-ritonavir (also known by its brand name ‘Paxlovid’). Nirmatrelvir-ritonavir was first recommended by WHO in April 2022. WHO strongly recommends its use in mild or moderate COVID-19 patients who are at high risk of hospitalization. 

Pregnant or breastfeeding women with non-severe COVID-19 should consult with their doctor to determine whether they should take this drug, due to ‘likely benefits’ and a lack of adverse events having been reported.

WHO also reviewed the evidence on 2 other medicines, sotrovimab and casirivimab-imdevimab, and maintains strong recommendations against their use for treating COVID-19. These monoclonal antibody medicines lack or have diminished activity against the current circulating virus variants.

There are currently 6 proven treatment options for patients with COVID-19, 3 that prevent hospitalization in high-risk persons and 3 that save lives in those with severe or critical disease. Except for corticosteroids, access to other drugs remains unsatisfactory globally.

reference link : https://www.emro.who.int/media/news/information-note-on-new-covid-19-omicron-subvariant-xbb15.html

LEAVE A REPLY

Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.