About

Aaron Schmidt is the Director of the Harvard Program in Virology and an Associate Professor in the Department of Microbiology. Originally from Wisconsin, he moved to Massachusetts for his undergraduate, graduate, and postdoctoral studies, ultimately becoming a Bostonian while retaining his Midwestern sensibilities. He holds a Ph.D. in Virology from Harvard University, where he worked in the Harrison Lab. As the head of the Schmidt Lab, Aaron leads research efforts in virology, managing his team and their projects. Outside of his professional work, he enjoys watching television and B-rated horror films.

Research topics

• Biology
• Virology
• Immunology
• Cell biology
• Internal medicine
• Medicine
• Chemistry
• Biochemistry
• Genetics
• Obstetrics
• Pathology
• Cancer research
• Computational biology
• Molecular biology

Selected publications

• Neuraminidase-on-a-string nanoparticles probe how antigenic distance shapes elicited humoral immunity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-26

  preprintOpen accessSenior authorCorresponding

  Understanding how antigenic distance influences cross-reactive responses can inform vaccine design. Multivalent displays of viral proteins can improve B cell activation due to receptor cross-linking, and mosaic nanoparticles that incorporate variants can lead to cross-reactive B cell responses recognizing conserved epitopes. Here, we used the influenza virus neuraminidase to develop a neuraminidase-on-a-string platform displaying neuraminidase dimer pairs conjugated to a nanocarrier To systematically assess the influence of antigenic distance on humoral immunity, we paired H2N2 neuraminidase with either divergent H3N2 or H11N9 neuraminidases. We found that nanoparticle immunizations with heterologous antigens elicited sera with greater breadth and enhanced enzymatic inhibition relative to immunizations that incorporated a single neuraminidase strain. While sera reactivity for H2N2 neuraminidase was not impacted by inclusion of a second strain, strain-specific responses correlatively increased with the antigenic distance between neuraminidase components. These data show how neuraminidase strain selection for multivalent display immunizations influences elicited breadth and cross-reactivity, highlighting findings that may extend to other viral antigens.

  PublisherOA PDFDOI

• Conserved sites on the influenza H1 and H3 hemagglutinin recognized by human antibodies

  Science Advances · 2025-04-23 · 8 citations

  articleOpen accessSenior authorCorresponding

  Monoclonal antibodies (mAbs) targeting the influenza hemagglutinin (HA) can be used as prophylactics or templates for next-generation vaccines. Here, we isolated broad, subtype-neutralizing mAbs from human B cells recognizing the H1 or H3 HA "head" and a mAb engaging the conserved stem. The H1 mAbs bind the lateral patch epitope on HAs from 1933 to 2021 and a prepandemic swine H1N1 virus. We improved neutralization potency using directed evolution toward a contemporary H1 HA. Deep mutational scanning of four antigenically distinct H1N1 viruses identified potential viral escape pathways. For the H3 mAbs, we used cryo-electron microscopy to define their epitopes: One mAb binds the side of the HA head, accommodating the N133 glycan and a pocket underneath the receptor binding site; the other mAb recognizes an HA stem epitope that partially overlaps with previously characterized mAbs but with distinct antibody variable genes. Collectively, these mAbs identify conserved sites recognized by broadly-reactive mAbs that may be elicited by next-generation vaccines.

  PublisherDOI

• Cultural landscape management plan for Mare Island Naval Cemetery, California

  2025-03-21

  reportOpen access

  This project was undertaken to provide the US Department of Veterans Affairs National Cemetery Administration with a cultural landscape manage-ment plan for Mare Island Naval Cemetery. The approximately 2.5-acre cemetery is located in Vallejo, California, and contains more than 900 burials. Mare Island Naval Cemetery is part of the Mare Island Naval Ship-yard historic district, which was listed concurrently on the National Register of Historic Places and as a National Historic Landmark in 1975. The US Army Engineer Research and Development Center, Construction Engineering Research Laboratory (ERDC-CERL) was tasked with writing a cultural landscape management plan for Mare Island Naval Cemetery. Based upon the findings of the historic landscape inventory. Treatment recommendations were made to rehabilitate the historic landscape as well as to provide a sustainable plant list for the cemetery.

  PublisherOA PDFDOI

• Author response: Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses

  2025-08-26

  peer-reviewOpen access

  Vaccines are the most effective way to prevent many infectious diseases and millions of deaths worldwide every year. They work by training the immune system to react to a protein – the antigen – that is specific to a pathogen. In response, the body produces specific antibodies, large proteins that mark the invaders for destruction. This builds a memory of this particular pathogen, enabling them to fight future infections better. Some vaccines contain antigens, while others contain weakened or inactivated viruses or bacteria. Newer vaccines often contain a blueprint for producing antigens, such as DNA or RNA, instead of an antigen. Each year, the flu vaccine is updated to match the main flu strains in circulation. This is because the vaccine’s key component – the spike protein hemagglutinin (HA) – works best when it triggers antibodies that recognize and neutralize viruses with the same HA sequence. A major obstacle to creating a universal flu vaccine is that influenza viruses constantly mutate, weakening the match between the vaccine and the virus. The problem is made worse because vaccines tend to produce antibodies that target the very parts of HA that change most frequently. Repeated vaccination with the same flu shot (called vaccine boosting) was thought to strengthen the original immune response by increasing the number of antibodies targeting the same variable parts of HA. However, recent findings from studies on SARS-CoV-2 (the virus that causes COVID-19) suggest this is not always the case. Instead, repeated vaccination can both boost existing antibodies and generate new ones that target previously unrecognized regions of the antigen. This broader antibody response can help protect against variant viruses that share these newly recognized regions. Deng, Tang et al. tested whether this antibody broadening also occurs with repeated influenza vaccination. The researchers evaluated data from a group of people who received the same flu vaccine for four consecutive years between 2013 to 2016, which included the new 2009 pandemic strain that many had never encountered before. The analyses showed that over time, their antibody responses became more diverse and capable of recognizing flu viruses spanning almost a century of evolution. To understand how this happens, Deng, Tang et al. built a computational model to trace how a type of immune cell known as the B cells mature and diversify their antibody production after vaccination. The findings suggest that the broad antibody response during vaccination boosting is an inherent feature of the human immune system. The next step and challenge will be to harness the natural ability to broaden antibody responses for designing vaccines that can protect against strains that may emerge in the future. This could involve fine-tuning HA or other vaccine proteins to better guide the immune system toward producing a broadly protective set of antibodies. Importantly, this principle of immune broadening could apply to any vaccine antigen – not just influenza.

  PublisherDOI

• Veterans Administration fourth generation historic context

  2025-09-12

  report1st authorCorresponding

  The period of significance for fourth generation of Veterans Administration (VA) medical centers ranges from 1955 to 1977. This period encapsulates a surge of VA medical center construction with congressional funding, dating from the release of the 1955 congressional report Nonbed Betterments in Veterans Administration Hospitals—Need for Renovation and Construction to the adoption of the Veterans Administration Medical Facilities Acquisition Act of 1977. New medical centers constructed by the VA during this time may be eligible under Criterion A for their association with health care and medicine, specifically for education and research relationships with medical schools. These partnerships advanced therapies, technology, and hospital operation in support of the VA’s mission to provide quality medical care for veterans. VA medical centers were commonly built adjacent to or within medical school complexes. Fourth generation VA medical centers may be eligible under Criterion C for embodying distinctive architecture or landscape architecture characteristics of mid-century modern hospitals or representing an important contribution in a significant architect’s career. This report provides a comprehensive historic context for the design, construction, and operation of new fourth generation VA medical centers in support of Section 110 of the National Historic Preservation Act of 1966 (NHPA).

  PublisherDOI

• A modular platform to display multiple hemagglutinin subtypes on a single immunogen

  eLife · 2025-12-08

  articleOpen accessSenior author

  Next-generation influenza vaccines aim to elicit cross-reactive humoral responses to multiple influenza subtypes. Such increased breadth would not only improve seasonal vaccines but may afford ‘universal’ protection against influenza subtypes, including those with pandemic potential. Here, we describe a ‘beads-on-a-string (BOAS)’ immunogen that tandemly links up to eight distinct hemagglutinin (HA) head domains from circulating and non-circulating influenzas. These BOAS are immunogenic in the murine model and elicit comparable serum responses to each individual component. Notably, we also find that BOAS elicit cross-reactive responses to influenza subtypes not included in the immunizing immunogen. Furthermore, BOAS conjugation to protein-based ferritin nanoparticles does not significantly augment serum responses suggesting that our BOAS platform is sufficient for eliciting cross-reactive responses without off-target effects induced by the nanoparticle scaffold. Finally, vaccination with a mixture of the same HA head domains is not sufficient to elicit the same neutralization profile as the BOAS immunogens or nanoparticles. This mix-and-match immunogen design strategy is a robust platform for eliciting responses to multiple influenza subtypes via a single immunogen, and a potential platform for other viral glycoproteins.

  PublisherDOI

• SARS-CoV-2 infection protects against rechallenge in rhesus macaques

  UNC Libraries · 2025-05-03

  articleOpen access

  An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log₁₀ reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.

  PublisherDOI

• A modular platform to display multiple hemagglutinin subtypes on a single immunogen

  eLife · 2025-04-15

  preprintOpen accessSenior author

  Abstract Next-generation influenza vaccines aim to elicit cross-reactive humoral responses to multiple influenza subtypes. Such increased breadth would not only improve seasonal vaccines but may afford ‘universal’ protection against influenza subtypes including those with pandemic potential. Here, we describe a “beads-on-a-string” (BOAS) immunogen, that tandemly links up to eight distinct hemagglutinin (HA) head domains from circulating and non-circulating influenzas. These BOAS are immunogenic in the murine model and elicit comparable serum responses to each individual component. Notably, we also find that BOAS elicit cross-reactive responses to influenza subtypes not included in the immunizing immunogen. Furthermore, BOAS conjugation to protein-based ferritin nanoparticles does not significantly augment serum responses suggesting that our BOAS platform is sufficient for eliciting cross-reactive responses without off-target effects induced by the nanoparticle scaffold. Finally, vaccination with a mixture of the same HA head domains is not sufficient to elicit the same neutralization profile as the BOAS immunogens or nanoparticles. This mix-and-match immunogen design strategy is a robust platform for eliciting responses to multiple influenza subtypes via a single immunogen, and a potential platform for other viral glycoproteins.

  PublisherDOI

• High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-04 · 1 citations

  preprintOpen access

  Neutralizing antibodies provide rapid immune defense against infectious diseases, but are difficult to discover at scale because neutralization assays require live reporter cells and soluble monoclonal antibodies. Here we report Droplet Reporter Cell Testing for Neutralization (DrReCT-Neutralization) to screen antibody gene libraries for their ability to neutralize viral infections. We established the necessary engineered cell lines and validated the DrReCT screening platform using synthetic oligoclonal libraries, followed by an example discovery campaign that demonstrated scalable functional antibody data collection against viral diseases.

  PublisherOA PDFDOI

• Mill Springs Mill, Kentucky : a history and analysis

  2025-05-09

  reportOpen access

  The US Congress codified the National Historic Preservation Act (NHPA) of 1966, the nation’s most effective cultural resources legislation to date, mostly through establishing the National Register of Historic Places (NRHP). The NHPA requires federal agencies to address their cultural re-sources, which are defined as any prehistoric or historic district, site, building, structure, or object. Section 110 of the NHPA requires federal agencies to inventory and evaluate their cultural resources, and Section 106 requires them to determine the effect of federal undertakings on those eligible or potentially eligible for the NRHP or listed on the NRHP. The Mill Springs Mill is found in south-central Kentucky, within Wayne County, a county bordering Tennessee. The mill, spring pools, granary, and recreation area are owned by the US Army Corps of Engineers (USACE). The site has run as a grist mill ever since its construction in the 1800s but has also been given other purposes, such as a roadside park starting in 1949 until the late 1970s and then a USACE recreation area. The mill is listed on the NRHP, while the grounds are part of the Mill Springs Battlefield, which is on the NRHP and also a national historic landmark. This report provides a comprehensive historic context for the features and buildings at the Mill Springs Mill in support of Section 110 of the NHPA.

  PublisherOA PDFDOI

Recent grants

• Core A: Administrative Core

  NIH · $74.1M · 2011–2028

• Epitope focusing by molecular grafting of subdominant epitopes to achieve a universal-influenza vaccine

  NIH · $4.2M · 2019–2024

• Molecular Basis of Viral Infectivity

  NIH · $13.9M · 1983–2029

Frequent coauthors

• Blake M. Hauser

  University of North Carolina at Chapel Hill

  129 shared

• Jared Feldman

  Ragon Institute of MGH, MIT and Harvard

  119 shared

• Stephen C. Harrison

  Queen's University

  109 shared

• Timothy M. Caradonna

  Ragon Institute of MGH, MIT and Harvard

  87 shared

• Dan H. Barouch

  Harvard University

  66 shared

• Daniel Lingwood

  Ragon Institute of MGH, MIT and Harvard

  60 shared

• Galit Alter

  Moderna Therapeutics (United States)

  50 shared

• Goran Bajic

  Icahn School of Medicine at Mount Sinai

  48 shared

Labs

• The Schmidt LaboratoryPI

Education

• Ph.D. Virology

  Harvard University

  2011

• B.Sc. Biology

  Emmanuel College

  2005

• B.Sc. Chemistry

  Emmanuel College

  2005