ABSTRACT
Against the backdrop of the rapid global takeover and dominance of BA.1/BA.2 and subsequently BA.2.86 lineages, the emergence of a highly divergent SARS-CoV-2 variant warrants characterization and close monitoring. Recently, another such BA.2 descendent, designated BA.2.87.1, was detected in South Africa. Here, we show using spike-pseudotyped viruses that BA.2.87.1 is less resistant to neutralisation by prevailing antibody responses in Sweden than other currently circulating variants such as JN.1. Further we show that a monovalent XBB.1.5-adapted booster enhanced neutralising antibody titers to BA.2.87.1 by almost 4-fold. While BA.2.87.1 may not outcompete other currently-circulating lineages, the repeated emergence and transmission of highly diverged variants suggests that another large antigenic shift, similar to the replacement by Omicron, may be likely in the future.
ABSTRACT
Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly mutated BA.2.86 lineage and against the backdrop of pronounced immune imprinting, it is important to characterize the antibody responses following vaccination, particularly in the elderly. Here, we show that the monovalent XBB.1.5-adapted booster vaccination substantially enhanced both binding and neutralising antibody responses against a panel of variants, including BA.2.86, in an older population with four or more previous vaccine doses. Furthermore, neutralizing antibody titers to XBB.1.5 and BA.2.86 were boosted more strongly than titers to historical variants were. Our findings thereby suggest increased vaccine induced protection against both antigenically matched variants, as well as the more distant BA.2.86 variant, and support current vaccine policies recommending a monovalent XBB.1.5 booster dose to older individuals.
ABSTRACT
Background: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal Covid-19 among nursing homes residents. Methods: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort study with inclusion of nursing home residents in Sweden. We analyzed immunological and registry data collected from September 2021 with end of follow-up 31 August 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves. Findings: A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG among 2606 blood-sampled individuals and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted the levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the 30-day mortality was 9.1%. We found no indication that antibodies protected against infection with Omicron, but that the risk of death was correlated to levels of S-directed IgG below the 20th percentile. In contrast, the risk plateaued at population average above lower 35th percentile of S-binding IgG. Interpretation: In the absence of neutralizing antibodies that protection from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal Covid-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern. Funding: Swedish Research Council, SciLife, Knut and Alice Wallenberg Foundation and Vinnova.
Subject(s)
COVID-19ABSTRACT
Background Booster vaccine doses offer protection against severe COVID-19 caused by omicron but are less effective against infection. Characteristics such as serological correlates of protection, viral abundance, and clearance of omicron infection in triple vaccinated individuals are scarce. Methods We conducted a 4-week twice-weekly SARS-CoV-2 qPCR screening shortly after an mRNA vaccine booster in 368 healthcare workers. Spike-specific IgG levels and neutralization titers were determined at study start. qPCR-positive participants were sampled repeatedly for two weeks and monitored for symptoms. Result In total 81 (cumulative incidence 22%) omicron infections were detected, divided between BA.1, BA.1.1 and BA.2. Increasing post-booster antibody titers were protective against infection (p<0.05), linked to reduced viral load (p<0.01) and time to viral clearance (p<0.05). Only 10% of infected participants remained asymptomatic through the course of their infection. Viral load peaked at day 3 and live virus could be detected for up to 9 days after first PCR-positive sample. Presence of symptoms correlated to elevated viral load (p<0.0001), but despite resolution of symptoms most participants showed Ct levels <30 at day 9. No significant differences were observed for viral load and time to viral clearance between BA.1, BA.1.1 and BA.2 infected individuals. Conclusion We report a high incidence of omicron infection despite recent booster vaccination in triple vaccinated individuals. Increasing levels of vaccine-induced spike-specific WT antibodies entail increased protection against infection and reduce viral load if infected. High viral load and secretion of live virus for up to nine days may facilitate transmission in a triple vaccinated population.