Publications by authors named "Anthony S Fauci"

The global experiences with the HIV/AIDS and COVID-19 pandemics hold important lessons for preparing for, and responding to, future outbreaks of emerging or re-emerging infectious diseases. Scores of infectious diseases have emerged or re-emerged over the past four decades, and future outbreaks are inevitable. The next emerging pathogen likely will again come from unanticipated sources and pose puzzles in terms of microbiology, transmission, natural history, pathogenesis, epidemiology, and will present challenges to developing countermeasures such as diagnostics, therapeutics, and vaccines.

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Article Synopsis
  • The emergence of SARS-CoV-2 required a faster vaccine development method than traditional approaches, leading to an urgent need for innovation in vaccine technology.
  • This year's Nobel Prize in Physiology or Medicine honors the breakthroughs in mRNA vaccine technology that played a critical role in controlling the COVID-19 pandemic.
  • The success was achieved through a combination of fundamental biological research and advanced technology, which revolutionized how vaccines are designed and produced.
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What keeps me up at night.

Sci Transl Med

October 2023

The lessons of COVID-19 must be heeded if the world is to be prepared for the next emergent pathogen with pandemic potential.

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  • * They engineered chimeric proteins by fusing parts of the SARS-CoV-2 Spike protein with HIV-1 or SIV sequences to enhance their effectiveness in producing VLPs, leading to increased cell-surface expression.
  • * Mice immunized with the mRNA showed significantly higher antibody responses against the Spike protein and maintained effectiveness against various SARS-CoV-2 variants, suggesting the Gag/VLP mRNA platform's potential for creating vaccines against multiple infectious diseases.
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On November 7th and 8th, 2022, The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), The Coalition for Epidemic Preparedness Innovation (CEPI), The Bill & Melinda Gates Foundation (BMGF), The Biomedical Advanced Research and Development Authority (BARDA), and the Wellcome Trust hosted a virtual workshop entitled “Mucosal Vaccines for SARS-CoV-2: Scientific Gaps and Opportunities.” During the workshop, researchers and vaccine developers from around the world discussed the potential of mucosal vaccines to block SARS-CoV-2 transmission and reviewed the status of SARS-CoV-2 mucosal vaccine research. Here, we summarize key challenges and opportunities in basic, translational, and clinical research that were highlighted during the meeting.

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The global experience with COVID-19 holds important lessons for preparing for, and responding to, future emergences of pathogens with pandemic potential.

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CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-β, promote the differentiation of CD4+ T cells into a distinct subset α4β7+CD69+CD103+ TRM-like cells.

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Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other "common cold" viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines, emphasizing that all of these viruses replicate extremely rapidly in the surface epithelium and are quickly transmitted to other hosts, within a narrow window of time before adaptive immune responses are fully marshaled.

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Article Synopsis
  • * In a study of 100 hospitalized COVID-19 patients, 95% tested positive for antibodies against PF4-polyanion complexes, with higher levels observed in males and certain racial groups compared to others.
  • * Elevated anti-PF4 antibodies were linked to more severe disease and lower platelet counts, but levels returned to normal in recovery; however, these antibodies didn't correlate with increased platelet activation from patient sera.
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SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories.

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SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a two-month period, we evaluated antibody and B-cell responses to a third dose mRNA vaccine in 66 individuals with different infection histories.

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Article Synopsis
  • - The emergence of SARS-CoV-1 20 years ago led to multiple global infectious disease outbreaks, highlighting the need for effective preparedness against future pandemics like SARS-CoV-2.
  • - In December 2021, the NIAID released a pandemic preparedness plan that focuses on research around key pathogens and technologies to foster rapid response to health crises.
  • - Adopting a prototype pathogen strategy can enhance research efforts and help develop medical countermeasures for new or reemerging infectious diseases, ultimately safeguarding public health.
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  • mRNA vaccines for SARS-CoV-2 effectively stimulate immune responses, but some individuals show weaker antibody responses, indicating a need for deeper understanding of B cell immunity.
  • The study analyzed B cell responses in individuals receiving the mRNA-1273 vaccine, highlighting that antibody levels were associated with the frequency of early plasmablasts after vaccination.
  • Two distinct populations of memory B cells (MBCs) were identified after vaccination, correlating with antibody levels at 2 and 6 months, suggesting these cells significantly influence the strength and longevity of the immune response.
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Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV). However, eradication of the virus in individuals with HIV has not been possible to date. Given that HIV suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication.

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The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in inducing neutralizing antibodies.

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The 2005 Immunity paper by Karikó et al. has been hailed as a cornerstone insight that directly led to the design and delivery of the mRNA vaccines against COVID-19. We asked experts in pathogen sensing, vaccine development, and public health to provide their perspective on the study and its implications.

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