High peak viraemia followed by spontaneous HIV-1 control in women living with HIV-1 subtype A1 in East Africa.

Introduction: Cases of spontaneous control of HIV-1 can help define strategies to induce remission. Since the identification of viral control in the absence of treatment typically occurs after a prolonged period post-HIV-1 diagnosis, our knowledge of the early events after HIV-1 acquisition that led to viral control is limited.

Methods: The RV217 prospective cohort enrolled 2276 participants in East Africa (Kenya, Uganda, Tanzania) and Thailand between 2009 and 2015.

Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts.

Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing.

NK cell activation and CD4+ T cell α4β7 expression are associated with susceptibility to HIV-1.

We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK cells, conventional T cells, and unconventional T cells influence HIV-1 acquisition. We observed low levels of α4β7 expression on memory CD4+ T cells and invariant NK T (iNKT) cells, 2 cell types highly susceptible to HIV-1 infection, in highly exposed seronegative (HESN) compared with highly exposed seroconverter (HESC) participants. NK cells from HESN individuals had higher levels of α4β7 than did those from HESC individuals, presented a quiescent phenotype, and had a higher capacity to respond to opsonized target cells.

Ebola virus vaccination elicits Ebola virus-specific immune responses without substantial cross-reactivity to other filoviruses.

The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis of antibody-mediated and cellular immune responses induced after two immunizations with either vaccine used first.

Impaired creatinine-based estimated glomerular filtration rate in Thai individuals switching to dolutegravir: illustrating the role of cystatin C testing to aid clinical decision making.

Introduction: Data about impact of switch to dolutegravir (DTG)-based antiretroviral therapy (ART) on estimated glomerular filtration rate (eGFR) in Asians are scarce. RV254/SEARCH010 is a prospective observational cohort in Bangkok, Thailand with ART initiation during acute HIV infection (AHI) where participants switched to DTG-based ART.

Methods: Participants started Efavirenz (EFV)-based ART during AHI (n = 214) and switched to DTG-based ART after a median of 97 weeks (IQR 61-145).

CD16 and CD57 expressing gamma delta T cells in acute HIV-1 infection are associated with the development of neutralization breadth.

New HIV vaccine approaches are focused on eliciting broadly neutralizing antibodies. We characterized early gamma-delta (γδ) T cell responses starting from pre-acquisition and during acute HIV infection (AHI) in participants previously characterized for neutralization breadth development. We found significant differences in γδ T cell surface marker expression in participants that developed neutralization breadth compared to those that did not.

Vaccine efficacy of NVX-CoV2373 against SARS-CoV-2 infection in adolescents in the USA: an ancillary study to a phase 3, observer-blinded, randomised, placebo-controlled trial.

Background: Although existing COVID-19 vaccines are known to be highly effective against severe disease and death, data are needed to assess their ability to reduce SARS-CoV-2 infection. We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents.

Methods: We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA.

Single-cell analyses reveal that monocyte gene expression profiles influence HIV-1 reservoir size in acutely treated cohorts.

Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq).

Prospective longitudinal study of men who have sex with men and transgender women to determine HIV incidence in two provinces in Thailand.

Background: In Thailand, HIV transmission is well characterized in large urban centers such as Bangkok and Chiang Mai but less so outside of these areas. The main purpose of this study was to assess HIV incidence and associated risk factors in Nakhon Ratchasima and Ratchaburi.

Methods: Participants assigned male sex at birth were enrolled in this prospective observational cohort study between November 2017 and July 2018.

HIV incidence and its associated factors among young adults with multiple sexual partners in Maputo, Mozambique: a vaccine preparedness study.

Introduction: Sub-Saharan Africa has a high burden of HIV, particularly among female sex workers (FSW) and men who have sex with men (MSM). Future clinical trials to evaluate vaccines and other interventions to prevent HIV will need to enroll populations with high HIV incidence. We conducted an observational study of HIV incidence among men and women with multiple sexual partners-including MSM and FSW-in Maputo, Mozambique, in order to prepare the country to conduct future efficacy trials of candidate HIV vaccines and other HIV prevention products.

Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial.

Background: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies.

Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial.

The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.

Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy.

Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.

SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

Background: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial.

Methods: In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 μg or 50 μg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181.

Safety and Immunogenicity of Accelerated Heterologous 2-Dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa.

Background: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.

Methods: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in 5 sub-Saharan African countries included people without human immunodeficiency virus (HIV) (PWOH, n = 249) and people with HIV (PWH, n = 250). Adult participants received 1 of 2 accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.

A remarkable genetic shift in a transmitted/founder virus broadens antibody responses against HIV-1.

A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists.

Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials.

Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015).

HIV prevalence and awareness among adults presenting for enrolment into a study of people at risk for HIV in Kisumu County, Western Kenya.

Introduction: Despite declines in new HIV diagnoses both globally and in Kenya, parts of Western Kenya still report high HIV prevalence and incidence. We evaluated HIV prevalence to inform the development of policies for strategic and targeted HIV prevention interventions.

Methods: Adult participants aged 18-35 years were recruited in Kisumu County and screened for HIV for a prospective HIV incidence cohort.

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study.

Background: The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the mechanisms remain unclear. The difficulty in elucidating the evolutionary origin of the earliest X4 viruses limits our understanding of this phenomenon.

Methods: We tracked the evolution of the transmitted/founder (T/F) HIV-1 in RV217 participants identified in acute infection.

Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study.

Background: The literature on first generation COVID-19 vaccines show they were less effective against new SARS-CoV-2 variants of concern including Omicron (BA.1, BA.2, BA.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort.

Initial productive and latent HIV infections originate in vivo by infection of resting T cells.

Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting CD4+ T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART).

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.