Biology subjects

Pinter, A.

Publications and source records attributed to Pinter, A..

3 recordsLinked to original sources

bioRxiv2021

Robust IgM responses following vaccination are associated with prevention of Mycobacterium tuberculosis infection in macaques

Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis (Mtb). However, recent work has shown that compared to standard intradermal Bacille Calmette-Guerin (BCG) vaccination, intravenous (IV) BCG vaccination provides nearly complete protection against TB in rhesus macaques. While studies have focused on cellular immunity in this setting, the antibody response elicited by IV BCG vaccination remains incompletely defined. Using an agnostic antibody profiling approach, here we show that IV BCG drives superior antibody responses in the plasma and the bronchoalveolar lavage fluid (BAL). While IV BCG immunization resulted in the expansion of a robust IgM, IgG, IgA, Fc-receptor binding antibodies, and antibody effector functions in the BAL, IgM titers were among the strongest markers of reduced bacterial burden in the plasma and BAL of BCG immunized animals. Moreover, IgM immunity was also enriched among animals receiving protective vaccination with an attenuated Mtb strain. Finally, a LAM-specific IgM monoclonal antibody reduced Mtb survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and as a functional mediator of protection against TB.

immunology↗

bioRxiv2021

Isolation and Purification of Lipoarabinomannan from Urine of Adults with Active Tuberculosis

Lipoarabinomannan (LAM) is a cell wall component of Mycobacterium tuberculosis that is excreted in the urine of persons with active tuberculosis (TB). Limited diagnostic sensitivity of LAM immunoassays has been due to selecting antibodies against LAM derived from in vitro cultured M. tuberculosis, rather than LAM purified from in vivo clinical urine specimens. Urinary LAM (uLAM) is critical to enable the development of and/or screening of novel uLAM-specific antibodies but is typically dilute and in heterogeneous mixtures with other urine components. We used physical, enzymatic, and chemical processes for the scaled isolation and purification of uLAM. The purified material may then be used to develop more sensitive uLAM diagnostic tests for active TB disease.

microbiology↗

bioRxiv2021

CAR-NK Cells Effectively Target the D614 and G614 SARS-CoV-2-infected Cells

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious presenting a significant public health issue. Current therapies used to treat coronavirus disease 2019 (COVID-19) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants, though the current therapeutic options remain limited and expensive. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of SARS-CoV-2 infection. However, their long-term side effects are not yet to be documented, and populations with immunocompromised conditions (e.g., organ-transplantation and immunodeficient patients) may not be able to mount an effective immune response. In addition, there are concerns that wide-scale immunity to SARS-CoV-2 may introduce immune pressure that could select for escape mutants to the existing vaccines and monoclonal antibody therapies. Emerging evidence has shown that chimeric antigen receptor (CAR)- natural killer (NK) immunotherapy has potent antitumor response in hematologic cancers with minimal adverse effects in recent studies, however, the potentials of CAR-NK cells in preventing and treating severe cases of COVID-19 has not yet been fully exploited. Here, we improve upon a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2 and its D614G mutant. CAR-NK cells were generated using the scFv domain of S309 (henceforward, S309-CAR-NK), a SARS-CoV and SARS-CoV-2 neutralizing antibody that targets the highly conserved region of SARS-CoV-2 spike (S) glycoprotein, therefore would be more likely to recognize different variants of SARS-CoV-2 isolates. S309-CAR-NK cells can specifically bind to pseudotyped SARS-CoV-2 virus and its D614G mutant. Furthermore, S309-CAR-NK cells can specifically kill target cells expressing SARS-CoV-2 S protein in vitro and show superior killing activity and cytokine production, compared to that of the recently published CR3022-CAR-NK cells. Thus, these results pave the way for generating off-the-shelf S309-CAR-NK cells for treatment in high-risk individuals as well as provide an alternative strategy for patients unresponsive to current vaccines.

immunology↗