About

Akiko Iwasaki, PhD, is a Sterling Professor of Immunobiology at Yale University School of Medicine, with additional appointments in Dermatology, Molecular, Cellular, and Developmental Biology, and Epidemiology (Microbial Diseases). Her research focuses on understanding how viruses infect hosts through mucosal surfaces, how the immune system responds to viral infections within these tissues, and how acute infections can lead to long-term diseases. Her work includes studying immune responses to various viruses such as herpes simplex, Zika, influenza, rhinoviruses, retroviruses, and notably SARS-CoV-2. Her research has contributed to the development of mucosal vaccines aimed at preventing infection, transmission, and recurrent diseases. She investigates mechanisms of innate immune recognition of viruses and the initiation of adaptive immunity at the natural sites of virus encounter, with the goal of informing better vaccine design and understanding the downstream consequences of immune failure, including infectious diseases, autoimmunity, neurodegenerative diseases, and cancer.

Research topics

• Medicine
• Biology
• Immunology
• Virology
• Internal medicine
• Genetics
• Pathology
• Chemistry
• Cancer research
• Computational biology
• Environmental health
• Obstetrics
• Oncology

Selected publications

• Insights Gained in the Hunt for Genital Herpes Vaccines

  2026-03-30

  article1st authorCorresponding

  Genital herpes, caused by Herpes Simplex Virus type 2 (HSV-2) and increasingly HSV-1, infects approximately half a billion people globally, often causing asymptomatic, recurrent disease and potentially contributing to dementia. Despite its prevalence, we do not have an effective vaccine against HSV-2, largely because it fails to elicit robust local mucosal immunity or to overcome viral immune evasion mechanisms. This study explores novel vaccination strategies by investigating the immune responses crucial for protection against genital herpes. Using mouse models, it was demonstrated that tissue-resident memory T cells (TRM) in the genital mucosa are essential for 100% protection against disease, secreting interferon-γ to block viral replication. CD4 T cells were found to initiate CD8 T cell migration to the mucosa via interferon-γ- induced chemokines (CXCL9, CXCL10) that bind to CXCR3. A "prime and pull" strategy was developed that combined systemic immunization with local delivery of chemokines to recruit virus-specific CD8 TRM cells. This approach protected mice from primary challenge and therapeutically reduced recurrent disease in guinea pigs, notably by engaging dendritic cells for antigen presentation, thereby circumventing HSV's MHC evasion. Further investigation revealed that CD4 T cells are critical for antibody access to neural tissues, the dorsal root ganglia (DRG), potentially by modulating blood-nerve barrier permeability through interferon-γ secretion, thereby blocking viral replication and latency establishment. Building on these insights, a novel nanoparticle system, BEACONs (bioactive enhanced adjuvant chemokine oligonucleotide nanoparticles), was engineered. Intravaginal BEACON delivery following an mRNA prime achieved 100% protection in mice, significantly reducing viral load in both the vaginal fluid and DRG for over 180 days, surpassing the efficacy of conventional prime-boost approaches. These findings underscore the importance of localized mucosal immunity and chemokine-driven cellular recruitment for effective and long-lasting protection against herpes simplex virus.

  PublisherDOI

• Mild SARS-CoV-2 maternal infection in mice induces transient offspring neurodevelopmental aberrance

  Proceedings of the National Academy of Sciences · 2026-03-18

  articleOpen accessSenior author

  Maternal viral infection during pregnancy has been identified as a risk factor for psychiatric disorders and neurodevelopmental abnormalities in offspring. With cumulative SARS-CoV-2 infections now numbering in the hundreds of millions globally, there is a need to evaluate the effects of maternal SARS-CoV-2 infection on offspring brain development and behavior. We developed a mouse model of mild COVID-19 during pregnancy in which SARS-CoV-2 infection is restricted to the respiratory tract. Infected mothers did not show weight loss or changes in litter size, but did exhibit detectable local and systemic immune responses, including placental inflammation. Characterization of the offspring's cerebral cortex revealed transcriptomic changes in the fetus at E15 and on postnatal day 5 (P5), but no gross alterations in cytoarchitecture, synaptic density, or microglial abundance. We did not detect any significant changes in open-field or novel object recognition tests in P50 offspring born to SARS-CoV-2-infected dams. These findings suggest that mild maternal respiratory SARS-CoV-2 infection induces soluble factors that mediate placental inflammation and transient cerebral cortex alterations in offspring that resolve by later childhood.

  PublisherDOI

• Freedom of scientific inquiry: reclaiming space for controversy

  Nature reviews. Immunology · 2026-05-01

  article1st authorCorresponding
  PublisherDOI

• Intranasal Anti-CD3 Antibody Treatment Attenuates Post–COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-08

  articleOpen accessSenior authorCorresponding

  Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-κB-driven inflammatory state toward chemokine signaling, phagosome, and TGF β-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.

  PublisherDOI

• Table S1 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma

  2025-12-10

  articleOpen access

  <p>Supplementary Table S1: Genomic and clinical characteristics of the study cohort.</p>

  PublisherDOI

• HKU5 bat merbecoviruses engage bat and mink ACE2 as entry receptors

  UNC Libraries · 2025-07-31

  articleOpen access

  Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness. While Middle East respiratory syndrome coronavirus (MERS-CoV) uses DPP4 for entry, the receptors of many MERS-related betacoronaviruses remain unknown. The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells. Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2, revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use and underscore the need for continued surveillance of bat and mustelid species.

  PublisherDOI

• Table S3 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma

  2025-12-10

  articleOpen access

  <p>Supplementary Table S3: Predicted pathogenic/deleterious variants by exome sequencing.</p>

  PublisherDOI

• COVID-19-associated neurological and psychological manifestations

  Nature Reviews Disease Primers · 2025-12-24 · 9 citations

  article
  PublisherDOI

• A causal link between autoantibodies and neurological symptoms in long COVID 2133

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a > 21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reporte Funding Sources This work was supported by the Else Kröner Fresenius Prize for Medical Research 2023, grants from the National Institute of Allergy and Infectious Diseases (R01AI157488 to A.I.), the Howard Hughes Medical Institute (A.I.). K.S.G.S. receive research support from Pew Latin American Fellowship. Topic Categories Neuroimmunology (NEUR)

  PublisherOA PDFDOI

• Table S4 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma

  2025-12-10

  articleOpen access

  <p>Supplementary Table S4: Metadata annotations for the scRNA-seq dataset.</p>

  PublisherDOI

Recent grants

• NIH Grant R21AI083242

  NIH · $453k · 2011

• Role of viral infections in potassium channel-related cerebellar ataxia

  NIH · $2.7M · 2019–2024

• NIH Grant R56AI125504

  NIH · $386k · 2017

• NIH Grant R01AI081884

  NIH · $2.0M · 2015

• Immunity to Genital Herpes Simplex-2

  NIH · $5.2M · 2003–2020

Frequent coauthors

• Albert I. Ko

  Yale University

  149 shared

• Eric Song

  Yale University

  123 shared

• Shelli Farhadian

  Yale University

  116 shared

• Tianyang Mao

  Yale University

  109 shared

• Charles S. Dela Cruz

  Yale University

  102 shared

• Nathan D. Grubaugh

  Yale University

  99 shared

• Arnau Casanovas‐Massana

  Yale University

  92 shared

• Wade L. Schulz

  Yale University

  91 shared

Education

• Ph.D., Immunobiology

  Yale University

  1990

• M.D.

  Yale University School of Medicine

  1985

• B.A., Biology

  Yale University

  1981

Awards & honors

• Keio Medical Science Prize in 2025
• Forbes 50 over 50 Innovation 2024
• TIME 100 Most Influential People 2024
• TIME 100 HEALTH Most Influential People Affecting Global Hea…
• Else Kröner Fresenius Prize for Medical Research 2023