Characterizing SARS-CoV-2 Neutralization Profiles After Bivalent Boosting Using Antigenic Cartography

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Aug 26

PMID 37633965

Authors

Annika Rossler

Antonia Netzl

Ludwig Knabl

David Bante

Samuel H Wilks

Wegene Borena

Dorothee von Laer

Derek J Smith

Janine Kimpel

Affiliations

Soon will be listed here.

Abstract

Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants.

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References

Davis-Gardner M, Lai L, Wali B, Samaha H, Solis D, Lee M . Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster. N Engl J Med. 2022; 388(2):183-185. PMC: 9812288. DOI: 10.1056/NEJMc2214293. View

Collier A, Miller J, Hachmann N, McMahan K, Liu J, A Bondzie E . Immunogenicity of BA.5 Bivalent mRNA Vaccine Boosters. N Engl J Med. 2023; 388(6):565-567. PMC: 9847505. DOI: 10.1056/NEJMc2213948. View

Freed N, Vlkova M, Faisal M, Silander O . Rapid and inexpensive whole-genome sequencing of SARS-CoV-2 using 1200 bp tiled amplicons and Oxford Nanopore Rapid Barcoding. Biol Methods Protoc. 2020; 5(1):bpaa014. PMC: 7454405. DOI: 10.1093/biomethods/bpaa014. View

Ewels P, Peltzer A, Fillinger S, Patel H, Alneberg J, Wilm A . The nf-core framework for community-curated bioinformatics pipelines. Nat Biotechnol. 2020; 38(3):276-278. DOI: 10.1038/s41587-020-0439-x. View

Wang W, Lusvarghi S, Subramanian R, Epsi N, Wang R, Goguet E . Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history. Cell Host Microbe. 2022; 30(12):1745-1758.e7. PMC: 9584854. DOI: 10.1016/j.chom.2022.10.012. View

Rossler A, Riepler L, Bante D, von Laer D, Kimpel J . SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons. N Engl J Med. 2022; 386(7):698-700. PMC: 8781314. DOI: 10.1056/NEJMc2119236. View

Wang W, Goguet E, Paz S, Vassell R, Pollett S, Mitre E . Bivalent Coronavirus Disease 2019 Vaccine Antibody Responses to Omicron Variants Suggest That Responses to Divergent Variants Would Be Improved With Matched Vaccine Antigens. J Infect Dis. 2023; 228(4):439-443. PMC: 10428200. DOI: 10.1093/infdis/jiad111. View

Riepler L, Rossler A, Falch A, Volland A, Borena W, von Laer D . Comparison of Four SARS-CoV-2 Neutralization Assays. Vaccines (Basel). 2020; 9(1). PMC: 7824240. DOI: 10.3390/vaccines9010013. View

Mykytyn A, Rissmann M, Kok A, Rosu M, Schipper D, Breugem T . Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct. Sci Immunol. 2022; 7(75):eabq4450. PMC: 9273038. DOI: 10.1126/sciimmunol.abq4450. View

10.

Hachmann N, Miller J, Collier A, Ventura J, Yu J, Rowe M . Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5. N Engl J Med. 2022; 387(1):86-88. PMC: 9258748. DOI: 10.1056/NEJMc2206576. View

11.

Winokur P, Gayed J, Fitz-Patrick D, Thomas S, Diya O, Lockhart S . Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years. N Engl J Med. 2023; 388(3):214-227. PMC: 9933930. DOI: 10.1056/NEJMoa2213082. View

12.

Rossler A, Netzl A, Knabl L, Schafer H, Wilks S, Bante D . BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants. Nat Commun. 2022; 13(1):7701. PMC: 9745279. DOI: 10.1038/s41467-022-35312-3. View

13.

Rossler A, Knabl L, von Laer D, Kimpel J . Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection. N Engl J Med. 2022; 386(18):1764-1766. PMC: 9006769. DOI: 10.1056/NEJMc2201607. View

14.

Viana R, Moyo S, Amoako D, Tegally H, Scheepers C, Althaus C . Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature. 2022; 603(7902):679-686. PMC: 8942855. DOI: 10.1038/s41586-022-04411-y. View

15.

Wang Q, Iketani S, Li Z, Liu L, Guo Y, Huang Y . Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. 2022; 186(2):279-286.e8. PMC: 9747694. DOI: 10.1016/j.cell.2022.12.018. View

16.

Smith D, Lapedes A, de Jong J, Bestebroer T, Rimmelzwaan G, Osterhaus A . Mapping the antigenic and genetic evolution of influenza virus. Science. 2004; 305(5682):371-6. DOI: 10.1126/science.1097211. View

17.

Li H . New strategies to improve minimap2 alignment accuracy. Bioinformatics. 2021; 37(23):4572-4574. PMC: 8652018. DOI: 10.1093/bioinformatics/btab705. View

18.

Carreno J, Alshammary H, Tcheou J, Singh G, Raskin A, Kawabata H . Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature. 2022; 602(7898):682-688. DOI: 10.1038/s41586-022-04399-5. View

19.

Branche A, Rouphael N, Losada C, Baden L, Anderson E, Luetkemeyer A . Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial. Clin Infect Dis. 2023; 77(4):560-564. PMC: 10443997. DOI: 10.1093/cid/ciad209. View

20.

Wilks S, Muhlemann B, Shen X, Tureli S, LeGresley E, Netzl A . Mapping SARS-CoV-2 antigenic relationships and serological responses. Science. 2023; 382(6666):eadj0070. DOI: 10.1126/science.adj0070. View