Archive for May 9, 2017

Humoral and Innate Antiviral Immunity as Tools to Clear Persistent HIV Infection

Journal of Infectious Diseases March 2017 V.215 Suppl.3

Guido Ferrari; Justin Pollara; Georgia D. Tomaras; Barton F. Haynes

Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells.

On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions.

HIV-1 Env-specific antibodies have the potential to bind HIV-1 cell surface Env and promote elimination of infected CD4+ T cells by recruiting cytotoxic effector cells, such as natural killer cells, monocytes, and polymorphonuclear cells.

Harnessing humoral and innate cellular responses has become one focus of research to develop innovative strategies to recruit and redirect cytotoxic effector cells to eliminate the HIV-1 latently infected CD4+ T-cell reservoir.

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May 9, 2017 at 8:20 am

EDITOR’S CHOICE – Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial

Journal of Infectious Diseases March 2017 V.215 N.6

David I. Bernstein; Anna Wald; Terri Warren; Kenneth Fife; Stephen Tyring

Background.

Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant.

Methods.

Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose.

Results.

One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses.

Conclusions.

GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates.

Clinical Trials Registration. NCT01667341 (funded by Genocea).

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Journal of Infectious Diseases March 2017 V.215 N.6

EDITOR’S CHOICE – Vaccination to Reduce Reactivation of Herpes Simplex Virus Type 2

Jeffrey I. Cohen

Herpes simplex virus type 2 (HSV-2) is associated with primary and recurrent genital herpes, disseminated disease or encephalitis in neonates, and severe disease in immunocompromised patients [1]. HSV-2 is also associated with an increased risk of acquisition and transmission of human immunodeficiency virus (HIV). More than 400 million persons are infected with HSV-2 worldwide, and there is no treatment to eliminate the virus….

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May 9, 2017 at 7:54 am

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