Publications by authors named "Amy R Henry"

Article Synopsis
  • - Our study reveals that HIV infection affects vaccine-induced immunity by reducing the effectiveness of specific CD4 T cells, linked to high levels of inflammatory signals and altered T cell composition.
  • - We discovered that the CD4 T cells from HIV-infected individuals show reduced expression of key genes associated with protective immunity from vaccines, along with impaired response pathways for important immune signals like IFNα and IFNγ.
  • - Importantly, reducing inflammation in HIV-infected patients using certain drugs improved the immune response of memory CD4 T cells, suggesting that managing inflammation could enhance vaccine efficacy in these individuals.
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An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID] ∼100) on a 208-strain panel.

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Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies.

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A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.

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Human immunodeficiency virus 1 (HIV-1) infection is characterized by a dynamic and persistent state of viral replication that overwhelms the host immune system in the absence of antiretroviral therapy (ART). The impact of prolonged treatment on the antiviral efficacy of HIV-1-specific CD8 T cells has nonetheless remained unknown. Here, we used single-cell technologies to address this issue in a cohort of aging individuals infected early during the pandemic and subsequently treated with continuous ART.

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Article Synopsis
  • - The study focuses on monitoring the evolution of SARS-CoV-2 variants to assess their ability to evade immune responses, emphasizing the importance of different neutralization assays and various serum samples.
  • - Comparisons were made among datasets using human, hamster, and mouse serum, revealing that animal models, especially hamsters, generally yielded higher neutralization titers than human samples, while showing consistent patterns across assays.
  • - The findings suggest a shift in SARS-CoV-2 surveillance strategies from relying solely on human serum from first infections to incorporating serum from animal models, particularly hamsters, for more reliable results.
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Norovirus infection can cause gastrointestinal disease in humans. Development of therapies and vaccines against norovirus have been limited by the lack of a suitable and reliable animal model. Here we established rhesus macaques as an animal model for human norovirus infection.

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Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV.

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Article Synopsis
  • Durable immunity against infections is linked to long-lived plasma cells (LLPCs) in the bone marrow, but their response to SARS-CoV-2 spike protein vaccination was previously unknown.
  • A new sensitive method was developed to identify and isolate these LLPCs, showing that two doses of the SARS-CoV-2 vaccine can create LLPC reservoirs in nonhuman primates that persist for several months.
  • Immunoglobulin gene sequencing revealed that these LLPCs are evolved clones of memory B cells, producing antibodies with improved effectiveness and cross-reactivity compared to earlier responses.
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SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.

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Article Synopsis
  • SARS-CoV-2 variants are evolving, making it crucial to test updated vaccines on non-human primates to improve human clinical practice.
  • Researchers conducted a study on mRNA-1273 vaccination in rhesus macaques, examining both innate and adaptive immune responses using single-cell sequencing.
  • They found that the second vaccine dose increased specific immune cells and gene expression linked to better antibody production, highlighting the interaction between innate and adaptive immunity.
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Article Synopsis
  • The engineered HIV gp120 outer domain germline-targeting version 8 (eOD-GT8) aims to activate naive B cell precursors that can produce VRC01-class antibodies, which are important for HIV protection.
  • While research on eOD-GT8's effects has focused on U.S. populations, this study investigates its recognition by naive B cells in sub-Saharan Africa, where HIV prevalence is much higher.
  • The findings reveal that individuals in sub-Saharan Africa either have a similar or higher frequency of naive B cells that can recognize eOD-GT8 compared to those in the U.S., suggesting that eOD-GT8 vaccination there could effectively boost CD4bs-directed memory B cell production.
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Waning immunity and continued virus evolution have limited the durability of protection from symptomatic infection mediated by intramuscularly (IM)-delivered mRNA vaccines against COVID-19 although protection from severe disease remains high. Mucosal vaccination has been proposed as a strategy to increase protection at the site of SARS-CoV-2 infection by enhancing airway immunity, potentially reducing rates of infection and transmission. Here, we compared protection against XBB.

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The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays.

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Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.

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Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups.

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Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling.

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Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Astrocytes are heterogeneous glial cells that are resident in the central nervous system and participate in the pathogenesis of multiple sclerosis and its model experimental autoimmune encephalomyelitis. However, few unique surface markers are available for the isolation of astrocyte subsets, preventing their analysis and the identification of candidate therapeutic targets; these limitations are further amplified by the rarity of pathogenic astrocytes.

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Article Synopsis
  • Infection with SARS-CoV-2 variants, like Beta, Gamma, and WA1, leads to the development of protective antibodies that can recognize multiple virus variants, including Delta and Omicron.
  • Researchers studied the types of antibodies produced in response to these infections and found a consistent pattern in their ability to bind to different viral variants, indicating a strong cross-reactive immune response.
  • The study also discovered that despite variations in the virus's antigens, similar gene usage and shared B cell clones were activated, suggesting that vaccines designed from a single ancestral variant can still effectively protect against newer strains.
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In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)-specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.

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Although combination antiretroviral therapy (ART) blocks HIV replication, it is not curative because infected CD4+ T cells that carry intact, infectious proviruses persist. Understanding the behavior of clones of infected T cells is important for understanding the stability of the reservoir; however, the stabilities of clones of infected T cells in persons on long-term ART are not well defined. We determined the relative stabilities of clones of infected and uninfected CD4+ T cells over time intervals of one to four years in three individuals who had been on ART for 9-19 years.

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Despite effective countermeasures, SARS-CoV-2 persists worldwide due to its ability to diversify and evade human immunity. This evasion stems from amino-acid substitutions, particularly in the receptor-binding domain of the spike, that confer resistance to vaccines and antibodies . To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different receptor binding domain (RBD) sites into multispecific antibodies.

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Antibody responses to the Pfizer-BioNTech mRNA vaccine waned substantially 6 months after the second vaccination.

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SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron.

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