Sigallab

Lab interests and highlights

1) We are interested in immune escape and changes in pathogenicity of SARS-CoV-2 variants. We we the first to characterize the immune escape of Omicron and were the first to isolate the live Beta variant.

2) We are interested in pathogen evolution and specifically the evolution of SARS-CoV-2 during long-term infection in immunosuppression. We have shown that immune escape mutations arise in SARS-CoV-2 during advanced HIV disease immunosuppression and are now looking at what other changes happen to the virus, including changes to mode of spread and pathogenicity.

3) We are interested in cell-to-cell spread strategies that pathogens use to overcome immunity. Relatedly, we are interested in compartmentalization of infection. Together, these factors may result in hard to eliminate infections, as we have shown for HIV cell-to-cell spread and compartmentalization in the brain. We have also shown serial killing of macrophages when they take up dead cells infected with aggregates of Mycobacterium tuberculosis, breaking the ability of these immune cells to contain the mycobacterial infection.

Lab PI and members

Alex Sigal is faculty at the Africa Health Research Institute and Associate Professor at the University of KwaZulu-Natal. Alex has a PhD in Systems Biology from the Weizmann Institute and was a postdoctoral fellow with David Baltimore at the California Institute of Technology. Sandile Cele, Farina Karim, and Khadija Khan, all from KwaZulu-Natal, South Africa, are PhD students in the lab and lead many of the projects. Lab staff are Yashica Ganga (Lab supervisor), Zesuliwe Jule (Technologist), Kajal Reedoy (Technologist), and Mallory Bernstein (Data Specialist).

Preprints

Beta infection combined with Pfizer BNT162b2 vaccination leads to broadened neutralizing immunity against Omicron. Manuscript.

Publications 2021-2022

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection. Nature Communications.

The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes. PLos Pathogens.

HIV viremia is associated with compromised SARS-CoV-2 Beta variant neutralization. J Infect. Dis.

Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition. eLife.

Omicron infection enhances Delta antibody immunity in vaccinated persons. Nature.

Estimating disease severity of Omicron and Delta SARS-CoV-2 infections Nature Reviews Immunology.

T cell responses to SARS-CoV-2 spike cross-recognize Omicron. Nature.

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature.

Milder disease with Omicron: is it the virus or the pre-existing immunity? Nature Reviews Immunology.

SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape. Cell Host & Microbe.

HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells Cell Reports.

Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature.

A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy. PLos Pathogens.

Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function. Molecular Biology and Evolution.

Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage. Nature Communications.

Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature.

Immunogenicity of SARS-CoV-2 infection and Ad26.CoV2.S vaccination in people living with HIV. Clin. Infect. Dis.

HIV status alters disease severity and immune cell responses in beta variant SARS-CoV-2 infection wave. eLife.

T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy. PLos Pathogens.

Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response. Frontiers.

Similar antibody responses against SARS-CoV-2 in HIV uninfected and infected individuals on antiretroviral therapy during the first South African infection wave. Clin Infect Dis.

Sixteen novel lineages of SARS-CoV-2 in South Africa. Nat Med.

Detection of a SARS-CoV-2 variant of concern in South Africa. Nature.

Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med.

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell.

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern. Nature Communications.

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology. Communications Biology.

Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strain. eLife.