HVTN 123: A Phase 1, Randomized Trial Comparing Safety and Immunogenicity of CH505TF gp120 Produced by Stably and Transiently Transfected Cell Lines.

Utilizing transiently transfected cell lines could significantly reduce manufacturing timelines for protein subunit vaccines. This trial compared safety and immunogenicity of human immunodeficiency virus (HIV) envelope CH505TF gp120 vaccines produced by upstream stable and transient transfection (each admixed with GLA-SE adjuvant, a TL4 agonist). Both vaccines were safe and well tolerated.

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119.

BACKGROUNDAn HIV-1 DNA vaccine composed of 7 highly conserved, structurally important elements (conserved elements, CE) of p24Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. DNA vaccination of CE prime/CE+p55Gag boost was compared with p55Gag.METHODSTwo groups (n = 25) received 4 DNA vaccinations (CE/CE+p55Gag or p55Gag) by intramuscular injection/electroporation, including IL-12 DNA adjuvant.

Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies.

A candidate antibody drug for prevention of malaria.

Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria.

The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy.

Objective: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).

Design: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4 + T-cell counts greater than 500 cells/μl, and nadir CD4 + T-cell counts greater than 350 cells/μl.

Methods: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55 Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55 Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C).

Pharmacokinetic serum concentrations of VRC01 correlate with prevention of HIV-1 acquisition.

Background: The phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, we investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data.

Methods: The case-control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study.

A simple model for viral decay dynamics and the distribution of infected cell life spans in SHIV-infected infant rhesus macaques.

The dynamics of HIV viral load following the initiation of antiretroviral therapy is not well-described by simple, single-phase exponential decay. Several mathematical models have been proposed to describe its more complex behavior, the most popular of which is two-phase exponential decay. The underlying assumption in two-phase exponential decay is that there are two classes of infected cells with different lifespans.

Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition.

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT) biomarker-which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate-can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses.

Maternal immune protection against infectious diseases.

The maternal immune system protects developing offspring against pathogens before birth via transplacental transfer and after birth through secreted milk. This transferred maternal immunity influences each generation's susceptibility to infections and responsiveness to immunization. Thus, boosting immunity in the maternal-neonatal dyad is a potentially valuable public health strategy.

E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2.

Diacetyl (DA) is an α-diketone that is used to flavor microwave popcorn, coffee, and e-cigarettes. Occupational exposure to high levels of DA causes impaired lung function and obstructive airway disease. Additionally, lower levels of DA exposure dampen host defenses in vitro.

Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection.

RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens.