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[Preprint]. 2021 Dec 7:2021.09.14.21263564.

doi: 10.1101/2021.09.14.21263564.

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

Sandile Cele^{1

2}, Farina Karim^{1

2}, Gila Lustig³, James Emmanuel San⁴, Tandile Hermanus^{5

6}, Houriiyah Tegally⁴, Jumari Snyman^{1

7}, Thandeka Moyo-Gwete^{1

2

3

4

5

6

7

8

9

10

11

12

13}, Eduan Wilkinson^{4

8}, Mallory Bernstein¹, Khadija Khan^{1

2}, Shi-Hsia Hwa^{1

9}, Sasha W Tilles¹⁰, Lavanya Singh⁴, Jennifer Giandhari⁴, Ntombifuthi Mthabela¹, Matilda Mazibuko¹, Yashica Ganga¹, Bernadett I Gosnell¹¹, Salim Abdool Karim³, Willem Hanekom^{1

9}, Wesley C Van Voorhis¹⁰, Thumbi Ndung'u^{1

7}; COMMIT-KZN Team; Richard J Lessells^{2

3

4}, Penny L Moore^{3

5

6}, Mahomed-Yunus S Moosa¹¹, Tulio de Oliveira^{2

3

4

8

12}, Alex Sigal^{1

2

13}

Affiliations

¹ Africa Health Research Institute, Durban, South Africa.
² School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
³ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
⁴ KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa.
⁵ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
⁶ MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.
⁸ HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa.
⁹ Division of Infection and Immunity, University College London, London, UK.
¹⁰ Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, USA.
¹¹ Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa.
¹² Department of Global Health, University of Washington, Seattle, USA.
¹³ Max Planck Institute for Infection Biology, Berlin, Germany.

PMID: 34909798
PMCID: PMC8669865
DOI: 10.1101/2021.09.14.21263564

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

Sandile Cele et al. medRxiv. 2021.

[Preprint]. 2021 Dec 7:2021.09.14.21263564.

doi: 10.1101/2021.09.14.21263564.

Authors

Affiliations

¹ Africa Health Research Institute, Durban, South Africa.
² School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
³ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
⁴ KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa.
⁵ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
⁶ MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.
⁸ HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa.
⁹ Division of Infection and Immunity, University College London, London, UK.
¹⁰ Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, USA.
¹¹ Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa.
¹² Department of Global Health, University of Washington, Seattle, USA.
¹³ Max Planck Institute for Infection Biology, Berlin, Germany.

PMID: 34909798
PMCID: PMC8669865
DOI: 10.1101/2021.09.14.21263564

Update in

SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape.
Cele S, Karim F, Lustig G, San JE, Hermanus T, Tegally H, Snyman J, Moyo-Gwete T, Wilkinson E, Bernstein M, Khan K, Hwa SH, Tilles SW, Singh L, Giandhari J, Mthabela N, Mazibuko M, Ganga Y, Gosnell BI, Karim SSA, Hanekom W, Van Voorhis WC, Ndung'u T; COMMIT-KZN Team; Lessells RJ, Moore PL, Moosa MS, de Oliveira T, Sigal A. Cele S, et al. Cell Host Microbe. 2022 Feb 9;30(2):154-162.e5. doi: 10.1016/j.chom.2022.01.005. Epub 2022 Jan 14. Cell Host Microbe. 2022. PMID: 35120605 Free PMC article.

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.

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Figures

**Figure 1:. Neutralization distance between variants.**
(A) Infection waves and variant frequencies in South Africa. (B) Maximum-likelihood phylogenetic tree with evolved virus sequences (red) at 6 time-points in relation to 3883 global sequences with variants shown. (C-E) Neutralization of the Beta (C), Delta (D) and Alpha (E) virus compared to D614G ancestral virus by plasma from convalescent participants infected by ancestral strains (n=8). (F-G) Neutralization of the Delta (F) and Alpha (G) compared to Beta virus by plasma from Beta infections (n=9). (H-I) Neutralization of the Beta (H) and Alpha (I) compared to Delta virus by plasma from Delta infections (n=10). Experiments presented in panels C-I performed by a live virus neutralization assay (LVNA). (J) Neutralization of Beta compared to Delta virus same plasma as (I) using a pseudo-virus neutralization assay (PNA). Red horizontal line denotes most concentrated plasma tested. Numbers in black above each virus strain are geometric mean titers (GMT) of the reciprocal plasma dilution (FRNT50 for LVNA, ID50 for PNA) for 50% neutralization. Numbers in red denote fold-change in GMT between virus strain on the left and the virus strain on the right. p-Values are * <0.05–0.01; ** <0.01–0.001; *** < 0.001–0.0001, **** < 0.0001 as determined by the Wilcoxon rank sum test.

**Figure 2:. Mapping neutralization of variants and evolved virus.**
(A) Participant characteristics over 233 days from SARS-CoV-2 diagnosis: CD4 T cell count (cells/μL), SARS-CoV-2 by qPCR, virus outgrowth, and presence of anti-RBD IgG. Because IgG levels were close to the background for some timepoints, they were marked as borderline. (B) Majority and minority SARS-CoV-2 genotypes in the swab (day 0) and outgrowth (day 6 to 190). X-axis lists substitutions and deletions in spike sequence and positions where mutations are found in variants are highlighted. AF: allele frequency. (C) Cryo-EM structure of the SARS-CoV-2 spike protein. The mutations in day 190 isolated virus (D190) shown as red spheres. (D) Neutralization of day 6 isolated (D6), day 20 isolated (D20), and D190 virus by self-plasma collected days 6 to 216 and the ancestral D614G, Beta and Delta viruses with plasma collected day 216. (E-F) Neutralization of D6 (E) and D20 (F) relative to D190 virus by ancestral infection elicited plasma (n=8). (G) Neutralization of D190 compared to D614G by Pfizer BNT162b2 plasma (n=12). (H-I) Neutralization of D190 (H) and D6 (I) compared to D614G by ancestral plasma (n=8). (J-K) Neutralization of D190 (J) and D6 (K) compared to Beta by Beta plasma (n=9). (L-M) Neutralization of D190 (L) and D6 (M) compared to Delta by Delta plasma (n=10). Red horizontal line denotes most concentrated plasma tested. Numbers in black are GMT FRNT50. Numbers in red are fold-change in GMT between virus strain on left and right. p-values are * <0.05–0.01; ** <0.01–0.001, *** <0.001–0.0001 as determined by the Wilcoxon rank sum test. (N) Summary map (not to scale) of serological distances as measured by fold-decrease in neutralization. For clarity, Beta plasma neutralization of D6 not shown.

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References

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This is a preprint.

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

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SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

Authors

Affiliations

Update in

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