	US 11,913,962 B2
	Materials and methods for subjects at risk for viral reactivation
Krishna Komanduri, Miami, FL (US); Eric Wieder, Miami, FL (US); Jose Camargo, Miami, FL (US); and Erik Kimble, Miami, FL (US)
Assigned to UNIVERSITY OF MIAMI, Miami, FL (US)
Appl. No. 16/613,411
Filed by UNIVERSITY OF MIAMI, Miami, FL (US)
PCT Filed May 14, 2018, PCT No. PCT/US2018/032577 § 371(c)(1), (2) Date Nov. 13, 2019, PCT Pub. No. WO2018/213192, PCT Pub. Date Nov. 22, 2018.
Claims priority of provisional application 62/506,585, filed on May 15, 2017.
Prior Publication US 2020/0072848 A1, Mar. 5, 2020
Int. Cl. G01N 33/68 (2006.01)

CPC G01N 33/6863 (2013.01) [G01N 2333/03 (2013.01); G01N 2333/523 (2013.01); G01N 2333/525 (2013.01); G01N 2333/55 (2013.01); G01N 2333/57 (2013.01); G01N 2800/245 (2013.01)]

12 Claims

1. A method comprising:

(a) identifying or quantifying a risk for reactivation of a latent herpesviridae virus in an immune-compromised mammalian subject from measurement of a T cell subset from a blood sample isolated from the subject,

wherein the measurement of the T cell subset is obtained by

(i) exposing the T cells to one or more antigens from the latent herpesviridae virus, under conditions to stimulate a T cell immune response;

(ii) evaluating individual T cells to detect or measure expression of cytokines IL-2, IFNγ, TNFα, and MIP-1β in the individual T cells;

(iii) evaluating the individual T cells to detect or measure CD8 expression; and

quantifying T cells having a CD8-positive (CD8+), IL-2-positive (IL-2+), IFNγ-positive (IFNγ+), TNFα-positive (TNFα+), MIP-1β-positive (MIP-1β+) phenotype (“PHENOTYPE-P”) from the blood sample; and/or quantifying T cells having a CD8-positive (CD8+), IL-2-negative (IL-2−), IFNγ-positive (IFNγ+), TNFα-negative (TNFα−), MIP-1β-positive (MIP-1β+) phenotype (“PHENOTYPE-N”) from the blood sample,

wherein the quantifying comprises:

quantifying the T cells with the phenotype relative to total T cells analyzed, to generate a relative measure of the quantity of the T cells with the phenotype; and/or

calculating a relative percentage or ratio of PHENOTYPE-P T cells to PHENOTYPE-N T cells;

(b) identifying an elevated or high risk for reactivation of the virus in the subject from the measurement; and

(c) administering, to the subject identified as having the elevated or high risk of viral reactivation, a prophylaxis that comprises an antiviral chemotherapeutic agent, wherein said agent comprises Ganciclovir, Valganciclovir, Foscarnet, Cidofovir, Maribavir, Brincidofovir, or Letermovir.