Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters

Lasrado, Ninaad; Collier, Ai‐ris Y.; Miller, Jessica; Hachmann, Nicole P.; Liu, Jinyan; Sciacca, Michaela; Wu, Cindy; Anand, Trisha; Bondzie, Esther A.; Fisher, Jana; Mazurek, Camille; Patio, Robert C.; Powers, Olivia; Rodrigues, Stefanie L.; Rowe, Marjorie; Surve, Nehalee; Ty, Darren; Korber, Bette; Barouch, Dan H.

doi:10.1101/2023.01.22.525079

Cited by 48 publications

(53 citation statements)

References 6 publications

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“…The BA.5 breakthrough cohort exhibited significantly higher NAb titers at three months against all Omicron subvariants tested when compared to both monovalent and bivalent booster cohorts ( Figure 1B ). An approximately 2-fold drop in mean NAb titers was noted for the vaccine cohorts over the follow-up period of ∼2 months ( Figure 1C ), consistent with recent findings 5 . Interestingly, there was no discernible waning of antibody responses in the BA.5 breakthrough infection cases over the same observation period.…”

Section: Main Textsupporting

confidence: 89%

SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster

Wang

Bowen

Tam

et al. 2023

Preprint

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Bivalent mRNA vaccine boosters expressing Omicron BA.5 spike and ancestral D614G spike were introduced to attempt to boost waning antibody titers and broaden coverage against emerging SARS-CoV-2 lineages. Previous reports showed that peak serum neutralizing antibody (NAb) titers against SARS-CoV-2 variants following bivalent booster were similar to peak titers following monovalent booster. It remains unknown whether these antibody responses would diverge over time. We assessed serum virus-neutralizing titers in 41 participants who received three monovalent mRNA vaccine doses followed by bivalent booster, monovalent booster, or BA.5 breakthrough infection at one month and three months after the last vaccine dose or breakthrough infection using pseudovirus neutralization assays against D614G and Omicron subvariants (BA.2, BA.5, BQ.1.1, and XBB.1.5). There was no significant difference at one month and three months post-booster for the two booster cohorts. BA.5 breakthrough patients exhibited significantly higher NAb titers at three months against all Omicron subvariants tested compared against monovalent and bivalent booster cohorts. There was a 2-fold drop in mean NAb titers in the booster cohorts between one and three month time points, but no discernible waning of titers in the BA.5 breakthrough cohort over the same period. Our results suggest that NAb titers after boosting with one dose of bivalent mRNA vaccine are not higher than boosting with monovalent vaccine. Perhaps inclusion of D614G spike in the bivalent booster exacerbates the challenge posed by immunological imprinting. Hope remains that a second bivalent booster could induce superior NAb responses against emerging variants.

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Section: Main Textsupporting

confidence: 89%

SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster

Wang

Bowen

Tam

et al. 2023

Preprint

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“…Moreover, bebtelovimab (LY-CoV1404) and Evusheld (a combination of COV2-2196 and COV2-2130) were found to be inactive against XBB/XBB.1 [ 6 ] and XBB.1.5 [ 15 ]. Although XBB.1.5 escapes neutralizing antibody responses, a study by Lasrado et al has shown that the cross-reactive T-cell responses may continue to protect against severe disease [ 25 ]. Therefore, due to immune-escape-associated and infectivity-enhancing mutations, the XBB* and XBB.1.5 variants can eventually spread worldwide [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Outcomes of Laboratory-Confirmed SARS-CoV-2 Cases Infected With Omicron Subvariants and the XBB Recombinant Variant

Karyakarte¹,

Das²,

Dudhate³

et al. 2023

Cureus

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BackgroundSARS-CoV-2 has evolved to produce new variants causing successive waves of infection. Currently, six variants are being monitored by the World Health Organization that are replacing BA.5. These include BF.7 (BA.5 + R346T in spike), BQ.1 (and BQ.1.1, with BA.5 + R346T, K444T, N460K mutations in spike), BA.2.75 (including BA.2.75.2 and CH.1.1), and XBB (including XBB.1.5). BQ.1 and XBB variants are more immune evasive and have spread quickly throughout the world. Concerning the potential severity of infections caused by these variants, the present study describes the clinical characteristics and outcomes of these major variants in Maharashtra. MethodologyA total of 1,141 reverse transcriptase-polymerase chain reaction (RT-PCR)-positive SARS-CoV-2 samples, with a cycle threshold (Ct) value of less than 25, were processed for SARS-CoV-2 whole genome sequencing between July 10, 2022, and January 12, 2023. All corresponding demographic and clinical data were recorded and analyzed using Microsoft® Excel and Epi Info™. ResultsOut of the 1,141 samples sequenced, BA.2.75* (63.78%) was the predominant Omicron variant, followed by the XBB* (18.88%), BA.2.38* (4.94%), BA.5* (4.06%), BA.2.10* (3.51%), and BQ.1* (1.65%). A total of 540 cases were contacted telephonically, of whom 494 (91.48%) were symptomatic with mild symptoms. Fever (77.73%) was the most common symptom, followed by cold (47.98%), cough (42.31%), and myalgia and fatigue (18.83%). Of the 540 cases, 414 (76.67%) cases recovered at home, and 126 (23.33%) were institutionally quarantined/hospitalized. Among the home-isolated and hospitalized cases, 416 (99.76%) and 108 (87.80%), respectively, recovered with symptomatic treatment, while one (0.24%) and 15 (12.20%), respectively, succumbed to the disease. Out of the 540 cases, 491 (90.93%) were vaccinated with at least one dose of the COVID-19 vaccine, 41 (7.59%) were unvaccinated, and for eight (1.48%) cases, vaccination data was not available. ConclusionsThe current study indicates that the XBB* variant is causing mild disease in India. However, as XBB* possesses both immune-escape and infectivity-enhancing mutations, it has the potential to spread to other parts of the world rapidly. Further, anti-SARS-CoV-2 vaccination improves survival rates in COVID-19.

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“…Over the approximately 2-month follow-up period, mean NAb titres in both vaccine cohorts decreased approximately two-fold (or 50%) against all tested viruses (eg, 1218 to 509 for monovalent cohorts against BA.5 and 1553 to 835 for bivalent cohorts against BA.5; appendix p 8 ), consistent with findings published in 2023. 5 There was no discernible waning of antibody responses in the BA.5 breakthrough infection cases over the same observation period. This finding suggests that our vaccine cohorts were not affected by undetected breakthrough infections.…”

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confidence: 81%