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Article ; Online: Place-of-care manufacturing of gene therapies.

Adair, Jennifer E / Anthony-Gonda, Kim / Bayigga, Lois / Orentas, Rimas / Mutuluuza, Cissy Kityo / Mathews, Vikram / Dropulić, Boro

The Lancet. Haematology

2022 Volume 9, Issue 11, Page(s) e807–e808

MeSH term(s)	Humans ; Genetic Therapy ; Cell- and Tissue-Based Therapy
Language	English
Publishing date	2022-09-15
Publishing country	England
Document type	Journal Article
ISSN	2352-3026
ISSN (online)	2352-3026
DOI	10.1016/S2352-3026(22)00327-1
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Article ; Online: Ethical and practical considerations for cell and gene therapy toward an HIV cure: findings from a qualitative in-depth interview study in the United States.

Dubé, Karine / Kanazawa, John / Patel, Hursch / Louella, Michael / Sylla, Laurie / Sheehy, Jeff / Dee, Lynda / Taylor, Jeff / Adair, Jen / Anthony-Gonda, Kim / Dropulić, Boro / Sauceda, John A / Peluso, Michael J / Deeks, Steven G / Simoni, Jane

BMC medical ethics

2022 Volume 23, Issue 1, Page(s) 39

Abstract: Background: HIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to ... ...

Abstract	Background: HIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale. Methods: To elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants' perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure. Results: We interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions. Conclusion: Our study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers.
MeSH term(s)	Ethicists ; Genetic Therapy ; HIV Infections/prevention & control ; Humans ; Qualitative Research ; Research Personnel ; United States
Language	English
Publishing date	2022-04-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2041552-7
ISSN	1472-6939 ; 1472-6939
ISSN (online)	1472-6939
ISSN	1472-6939
DOI	10.1186/s12910-022-00780-1
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Article ; Online: Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models.

Schneider, Dina / Xiong, Ying / Wu, Darong / Hu, Peirong / Alabanza, Leah / Steimle, Brittany / Mahmud, Hasan / Anthony-Gonda, Kim / Krueger, Winfried / Zhu, Zhongyu / Dimitrov, Dimiter S / Orentas, Rimas J / Dropulić, Boro

Science translational medicine

2021 Volume 13, Issue 586

Abstract: A substantial number of patients with leukemia and lymphoma treated with anti-CD19 or anti-CD22 monoCAR-T cell therapy relapse because of antigen loss or down-regulation. We hypothesized that B cell tumor antigen escape may be overcome by a chimeric ... ...

Abstract	A substantial number of patients with leukemia and lymphoma treated with anti-CD19 or anti-CD22 monoCAR-T cell therapy relapse because of antigen loss or down-regulation. We hypothesized that B cell tumor antigen escape may be overcome by a chimeric antigen receptor (CAR) design that simultaneously targets three B cell leukemia antigens. We engineered trispecific duoCAR-T cells with lentiviral vectors encoding two CAR open reading frames that target CD19, CD20, and CD22. The duoCARs were composed of a CAR with a tandem CD19- and CD20-targeting binder, linked by the P2A self-cleaving peptide to a second CAR targeting CD22. Multiple combinations of intracellular T cell signaling motifs were evaluated. The most potent duoCAR architectures included those with ICOS, OX40, or CD27 signaling domains rather than those from CD28 or 4-1BB. We identified four optimal binder and signaling combinations that potently rejected xenografted leukemia and lymphoma tumors in vivo. Moreover, in mice bearing a mixture of B cell lymphoma lines composed of parental triple-positive cells, CD19-negative, CD20-negative, and CD22-negative variants, only the trispecific duoCAR-T cells rapidly and efficiently rejected the tumors. Each of the monoCAR-T cells failed to prevent tumor progression. Analysis of intracellular signaling profiles demonstrates that the distinct signaling of the intracellular domains used may contribute to these differential effects. Multispecific duoCAR-T cells are a promising strategy to prevent antigen loss-mediated relapse or the down-regulation of target antigen in patients with B cell malignancies.
Language	English
Publishing date	2021-03-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abc6401
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Article ; Online: Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine.

Cheung, Foo / Apps, Richard / Dropulic, Lesia / Kotliarov, Yuri / Chen, Jinguo / Jordan, Tristan / Langweiler, Marc / Candia, Julian / Biancotto, Angelique / Han, Kyu Lee / Rachmaninoff, Nicholas / Pietz, Harlan / Wang, Kening / Tsang, John S / Cohen, Jeffrey I

eLife

2023 Volume 12

Abstract: Background: Both sex and prior exposure to pathogens are known to influence responses to immune challenges, but their combined effects are not well established in humans, particularly in early innate responses critical for shaping subsequent outcomes.!## ...

Abstract	Background: Both sex and prior exposure to pathogens are known to influence responses to immune challenges, but their combined effects are not well established in humans, particularly in early innate responses critical for shaping subsequent outcomes. Methods: We employed systems immunology approaches to study responses to a replication-defective, herpes simplex virus (HSV) 2 vaccine in men and women either naive or previously exposed to HSV. Results: Blood transcriptomic and cell population profiling showed substantial changes on day 1 after vaccination, but the responses depended on sex and whether the vaccinee was naive or previously exposed to HSV. The magnitude of early transcriptional responses was greatest in HSV naive women where type I interferon (IFN) signatures were prominent and associated negatively with vaccine-induced neutralizing antibody titers, suggesting that a strong early antiviral response reduced the uptake of this replication-defective virus vaccine. While HSV seronegative vaccine recipients had upregulation of gene sets in type I IFN (IFN-α/β) responses, HSV2 seropositive vaccine recipients tended to have responses focused more on type II IFN (IFN-γ) genes. Conclusions: These results together show that prior exposure and sex interact to shape early innate responses that then impact subsequent adaptive immune phenotypes. Funding: Intramural Research Program of the NIH, the National Institute of Allergy and Infectious Diseases, and other institutes supporting the Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation. The vaccine trial was supported through a clinical trial agreement between the National Institute of Allergy and Infectious Diseases and Sanofi Pasteur. Clinical trial number: NCT01915212.
MeSH term(s)	Female ; Humans ; Male ; Antibodies, Neutralizing ; Herpesvirus 2, Human ; Herpesvirus Vaccines/immunology ; Immunity, Innate ; Vaccines, Attenuated ; Sex Factors ; Herpes Simplex/prevention & control
Chemical Substances	Antibodies, Neutralizing ; Herpesvirus Vaccines ; Vaccines, Attenuated
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.80652
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Article ; Online: In vivo killing of primary HIV-infected cells by peripheral-injected early memory-enriched anti-HIV duoCAR T cells.

JCI insight

2022 Volume 7, Issue 21

Abstract: HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. ... ...

Abstract	HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell-like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).
MeSH term(s)	Animals ; Mice ; CD4-Positive T-Lymphocytes ; HIV Infections/drug therapy ; HIV-1 ; Leukocytes, Mononuclear ; Receptors, Chimeric Antigen ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2022-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.161698
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Article ; Online: Update on new antivirals under development for the treatment of double-stranded DNA virus infections.

Dropulic, L K / Cohen, J I

Clinical pharmacology and therapeutics

2010 Volume 88, Issue 5, Page(s) 610–619

Abstract: All the currently available antiviral agents used in the treatment of double-stranded (ds) DNA viruses, with the exception of interferon-α, inhibit the same target, the viral DNA polymerase. With increasing reports of the development of resistance of ... ...

Abstract	All the currently available antiviral agents used in the treatment of double-stranded (ds) DNA viruses, with the exception of interferon-α, inhibit the same target, the viral DNA polymerase. With increasing reports of the development of resistance of herpes simplex virus (HSV), cytomegalovirus (CMV), and hepatitis B virus (HBV) to some of these drugs, new antiviral agents are needed to treat these infections. Additionally, no drugs have been approved to treat several DNA virus infections, including those caused by adenovirus, smallpox, molluscum contagiosum, and BK virus. We report the status of 10 new antiviral drugs for the treatment of dsDNA viruses. CMX-001 has broad activity against dsDNA viruses; 3 helicase-primase inhibitors, maribavir, and FV-100 have activity against certain herpesviruses; ST-246 inhibits poxviruses; GS-9191 inhibits papillomaviruses; and clevudine and emtricitabine are active against HBV. Most of these drugs have completed at least phase I trials in humans, and many are in additional clinical trials.
MeSH term(s)	Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Clinical Trials as Topic ; DNA Virus Infections/drug therapy ; DNA Virus Infections/virology ; DNA Viruses/drug effects ; DNA Viruses/genetics ; DNA, Viral ; Disease Models, Animal ; Drug Design ; Humans ; Nucleic Acid Conformation ; Treatment Outcome
Chemical Substances	Antiviral Agents ; DNA, Viral
Language	English
Publishing date	2010-09-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1038/clpt.2010.178
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Article ; Online: Comparison of Levels of Nasal, Salivary, and Plasma Antibody to Severe Acute Respiratory Syndrome Coronavirus 2 During Natural Infection and After Vaccination.

Cohen, Jeffrey I / Dropulic, Lesia / Wang, Kening / Gangler, Krista / Morgan, Kayla / Liepshutz, Kelly / Krogmann, Tammy / Ali, Mir A / Qin, Jing / Wang, Jing / Vogel, Joshua S / Lei, Yona / Suzuki-Williams, Lui P / Spalding, Chris / Palmore, Tara N / Burbelo, Peter D

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 76, Issue 8, Page(s) 1391–1399

Abstract: Background: Most studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) measure antibody or cellular responses in blood; however, the virus infects mucosal surfaces in the nose and conjunctivae and infectious virus is rarely ...

Abstract	Background: Most studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) measure antibody or cellular responses in blood; however, the virus infects mucosal surfaces in the nose and conjunctivae and infectious virus is rarely if ever present in the blood. Methods: We used luciferase immunoprecipitation assays to measure SARS-CoV-2 antibody levels in the plasma, nose, and saliva of infected persons and vaccine recipients. These assays measure antibody that can precipitate the SAR-CoV-2 spike and nucleocapsid proteins. Results: Levels of plasma anti-spike antibody declined less rapidly than levels of anti-nucleocapsid antibody in infected persons. SARS-CoV-2 anti-spike antibody levels in the nose declined more rapidly than antibody levels in the blood after vaccination of infected persons. Vaccination of previously infected persons boosted anti-spike antibody in plasma more than in the nose or saliva. Nasal and saliva anti-spike antibody levels were significantly correlated with plasma antibody in infected persons who had not been vaccinated and after vaccination of uninfected persons. Conclusions: Persistently elevated SARS-CoV-2 antibody in plasma may not indicate persistence of antibody at mucosal sites such as the nose. The strong correlation of SARS-CoV-2 antibody in the nose and saliva with that in the blood suggests that mucosal antibodies are derived primarily from transudation from the blood rather than local production. While SARS-CoV-2 vaccine given peripherally boosted mucosal immune responses in infected persons, the increase in antibody titers was higher in plasma than at mucosal sites. Taken together, these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs. Clinical trials registration: NCT01306084.
MeSH term(s)	Humans ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2022-12-08
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac934
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma.

Tian, Meijie / Wei, Jun S / Shivaprasad, Nityashree / Highfill, Steven L / Gryder, Berkley E / Milewski, David / Brown, G Tom / Moses, Larry / Song, Hannah / Wu, Jerry T / Azorsa, Peter / Kumar, Jeetendra / Schneider, Dina / Chou, Hsien-Chao / Song, Young K / Rahmy, Abdelrahman / Masih, Katherine E / Kim, Yong Yean / Belyea, Brian /

Linardic, Corinne M / Dropulic, Boro / Sullivan, Peter M / Sorensen, Poul H / Dimitrov, Dimiter S / Maris, John M / Mackall, Crystal L / Orentas, Rimas J / Cheuk, Adam T / Khan, Javed

Cell reports. Medicine

2023 Volume 4, Issue 10, Page(s) 101212

Abstract: Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and ... ...

Abstract	Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS. The 3A11 CAR T cells induced robust cytokine production and cytotoxicity against RMS cell lines in vitro. In contrast, a panel of healthy human primary cells failed to activate 3A11 CAR T cells, confirming the selectivity of 3A11 CAR T cells against tumors with high FGFR4 expression. Finally, we demonstrate that 3A11 CAR T cells are persistent in vivo and can effectively eliminate RMS tumors in two metastatic and two orthotopic models. Therefore, our study credentials CAR T cell therapy targeting FGFR4 to treat patients with RMS.
MeSH term(s)	Animals ; Child ; Humans ; Mice ; Cell Line, Tumor ; Immunotherapy, Adoptive ; Receptor, Fibroblast Growth Factor, Type 4/genetics ; Receptor, Fibroblast Growth Factor, Type 4/metabolism ; Receptors, Chimeric Antigen/genetics ; Rhabdomyosarcoma/drug therapy
Chemical Substances	FGFR4 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 4 (EC 2.7.10.1) ; Receptors, Chimeric Antigen
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101212
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Article: Polyomavirus BK infection in blood and marrow transplant recipients.

Dropulic, L K / Jones, R J

Bone marrow transplantation

2007 Volume 41, Issue 1, Page(s) 11–18

Abstract: The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, ... ...

Abstract	The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population.
MeSH term(s)	BK Virus ; Bone Marrow Transplantation/adverse effects ; Cystitis/diagnosis ; Cystitis/etiology ; Cystitis/therapy ; Hemorrhage/diagnosis ; Hemorrhage/etiology ; Hemorrhage/therapy ; Humans ; Polyomavirus Infections/etiology ; Tumor Virus Infections/etiology ; Viral Load
Language	English
Publishing date	2007-10-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/sj.bmt.1705886
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Zs.A 2168: Show issues

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Article ; Online: An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans.

Andrews, Sarah F / Cominsky, Lauren Y / Shimberg, Geoffrey D / Gillespie, Rebecca A / Gorman, Jason / Raab, Julie E / Brand, Joshua / Creanga, Adrian / Gajjala, Suprabhath R / Narpala, Sandeep / Cheung, Crystal S F / Harris, Darcy R / Zhou, Tongqing / Gordon, Ingelise / Holman, LaSonji / Mendoza, Floreliz / Houser, Katherine V / Chen, Grace L / Mascola, John R /

Graham, Barney S / Kwong, Peter D / Widge, Alicia / Dropulic, Lesia K / Ledgerwood, Julie E / Kanekiyo, Masaru / McDermott, Adrian B

Science translational medicine

2023 Volume 15, Issue 692, Page(s) eade4976

Abstract: Current yearly seasonal influenza vaccines primarily induce an antibody response directed against the immunodominant but continually diversifying hemagglutinin (HA) head region. These antibody responses provide protection against the vaccinating strain ... ...

Abstract	Current yearly seasonal influenza vaccines primarily induce an antibody response directed against the immunodominant but continually diversifying hemagglutinin (HA) head region. These antibody responses provide protection against the vaccinating strain but little cross-protection against other influenza strains or subtypes. To focus the immune response on subdominant but more conserved epitopes on the HA stem that might protect against a broad range of influenza strains, we developed a stabilized H1 stem immunogen lacking the immunodominant head displayed on a ferritin nanoparticle (H1ssF). Here, we evaluated the B cell response to H1ssF in healthy adults ages 18 to 70 in a phase 1 clinical trial (NCT03814720). We observed both a strong plasmablast response and sustained elicitation of cross-reactive HA stem-specific memory B cells after vaccination with H1ssF in individuals of all ages. The B cell response was focused on two conserved epitopes on the H1 stem, with a highly restricted immunoglobulin repertoire unique to each epitope. On average, two-thirds of the B cell and serological antibody response recognized a central epitope on the H1 stem and exhibited broad neutralization across group 1 influenza virus subtypes. The remaining third recognized an epitope near the viral membrane anchor and was largely limited to H1 strains. Together, we demonstrate that an H1 HA immunogen lacking the immunodominant HA head produces a robust and broadly neutralizing HA stem-directed B cell response.
MeSH term(s)	Adolescent ; Adult ; Aged ; Humans ; Middle Aged ; Young Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Influenza Vaccines ; Influenza, Human
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Influenza Vaccines
Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.ade4976
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