# data[].attributes.title
A novel shift-level approach to optimizing ICU interprofessional team composition for mechanically ventilated adults

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National Heart Lung and Blood Institute (NHLBI)

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At the core of critical care delivery is the interprofessional team, comprised of nurses, physicians, and respiratory therapists, who provide around-the-clock care to the most critically ill patients. The COVID-19 pandemic underscored the need for a robust critical care workforce and exposed existing structural inequities in the healthcare system. Research has shown disparities in mechanical ventilation (MV) care and outcomes based on patient characteristics, such as age and ethnicity. One evidence-based practice associated with improved outcomes for MV patients—spontaneous awakening and spontaneous breathing trials (SATs and SBTs)—requires effective coordination and collaboration among the entire team. For decades, researchers have sought to optimize the organization of critical care teams to enhance patient outcomes. While studies within individual professions, such as nurses or physicians, have examined the impact of clinician characteristics (e.g., experience) and scheduling characteristics (e.g., overtime) on outcomes, there remains a dearth of research investigating how variations in clinician and scheduling characteristics across the entire team influences patient outcomes. To address this knowledge gap, this application aims to determine how clinician and scheduling characteristics impact patient outcomes, and explore the moderating effect that clusters of patient characteristics have on the relationship between clinician and scheduling characteristics on patient outcomes. We propose a novel secondary analysis utilizing a unique dataset that links electronic health record data from nearly 17,000 critically ill patients to human resource clinician characteristics of 8,000 clinicians across 5 intensive care units from 2018-2021. Our specific aims are: 1) Test the hypothesis that patients cared for by teams with better clinician characteristics and scheduling characteristics will be more likely to receive SATs and SBTs each shift (when eligible), more likely to be extubated each shift, and less likely to die each shift. Among (n=8,952) MV patients, we will use a patient-level design and a longitudinal, repeat-measures analysis, where patients serve as their own control. 2) Evaluate the moderating effect of patient characteristics on the relationship between clinician and scheduling characteristics and patient outcomes. Among all ICU patients (N=16,940), we will use multiple interactions to identify what clusters of patient characteristics (e.g., age, sex, race, ethnicity) may be most vulnerable, i.e., experience negative outcomes, to variation in clinician and scheduling characteristics of the assigned team. If supported by our findings and replicated in a larger national study, then a patient-centered approach to ICU team assignments could be a cost-effective intervention that does not require additional staffing. This proposal has the potential to significantly transform the way interprofessional teams are assigned to ICU patients.

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National Heart  Lung  and Blood Institute

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Regulation and Function of respiratory mucosal immunity post SARS-CoV-2 vaccination and infection

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National Institute of Allergy and Infectious Diseases (NIAID)

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Current intramuscular COVID-19 vaccines, despite eliciting robust systemic immune responses, generate suboptimal neutralizing antibody (nAb), IgA Ab, and cellular responses in the respiratory mucosal. This is likely why current vaccines are less effective at preventing infection and transmission. The role of mucosal immunity in protecting against respiratory viral infection remains largely unexplored. The long-term goal of this research is to comprehensively understand the differentiation, function, regulation, and interaction of respiratory immune cells. Pilot data revealed that people with hybrid immunity from SARS-CoV-2 infection and vaccination exhibit significantly high levels of antigen-specific IgA and nAbs in the respiratory mucosa, compared to those who got vaccinated or infected alone. Further, recent research and our initial findings suggest that mucosal IgA is locally produced by lung-resident B cells during both primary infection and reinfection, yet the specific role and development of mucosal IgA are not fully understood. Therefore, the overall objectives of this application are to a) understand systemic and mucosal immunity in people with hybrid immunity, b) define immune compartments that confer protection and transmission in animal models, and c) unravel the mechanisms underlying the respiratory protection of mucosal immunity. The central hypothesis is that respiratory IgA provides neutralization and protection against heterologous infection, facilitated by an orchestrated interaction between macrophages, CD4 Th1 cells, and IgA+ B cells in the respiratory mucosa. This hypothesis will be tested by pursuing three specific aims: 1) To identify the respiratory mucosal immunity in people with hybrid immunity, 2) To study protection and transmission following SARS-CoV-2 breakthrough infection or mucosal vaccine booster in animal models primed with mRNA vaccines, and 3) To elucidate the mechanisms underlying the mucosal protection of respiratory immunity. Aim 1 will systematically profile the immune signatures in the blood, nasal cavity, and lower airway in children with hybrid immunity. Aim 2 will utilize mouse and hamster models of hybrid immunity and mucosal vaccine booster to study protection and transmission. Under Aim 3, we will investigate the mechanism of mucosal protection in both humans and mice. This research will advance our understanding of respiratory immunology and vaccinology, potentially impacting the global fight against SARS-CoV-2 and future respiratory viruses. This project will provide the applicant, Dr. Jinyi Tang, with experimental and conceptual training to develop his research program and ensure his transition to an independent tenure- track position. Dr. Tang will be mentored by a committee of experienced immunologist, virologist and clinician-scientist specializing in mucosal viral immunology, led by primary mentor Dr. Jie Sun. The planned career development activities will ensure Dr. Tang achieves his long-term goals of consistent manuscript publishing, achieving independent funding, and training of the next generation of scientists.

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The Role of Tunneling Nanotubes and Mitochondrial programming in HIV-Associated Placental Dysfunction

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National Institute of Allergy and Infectious Diseases (NIAID)

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/ ABSTRACT HIV is known to be transmissible from mother to the developing fetus during pregnancy, leading to adverse health outcomes for both. Although HIV is linked to placental pathologies, there is still a large gap in knowledge about the mechanisms underlying HIV-associated pregnancy complications, despite four decades of research in general on HIV topics. The objective of this project is to investigate the role of intercellular conduits composed of F-actin microtubules that connect plasma membranes of neighboring cells enabling cytoplasmic continuing and intercellular transfer of cargo. These conduits are known as tunneling nanotubes (TNTs). Recent investigations by the PI and others have demonstrated that other viruses such as Zika and SARS-CoV-2 induce the formation of TNTs in placental trophoblast cells, and there is evidence they serve as a means of mitochondrial transfer and possibly viral transfer that promotes infectious spread. There is evidence that HIV induces TNT formation in neurons, but it is not known whether the virus has this effect on placental cells. Building on prior studies and ongoing work by the PI, the central hypothesis of this project is that HIV uses TNTs to spread infection in trophoblasts, and that TNTs mediate placental dysfunction by transferring damaged mitochondria and adversely reprogramming trophoblast metabolism. This metabolic reprogramming may contribute to placental dysfunction and adverse pregnancy outcomes. Aim 1 of this project will elucidate the molecular mechanisms of TNT formation between HIV-infected immune cells and trophoblasts. Aim 2 will determine the impact of HIV on mitochondrial dynamics and transfer and resulting trophoblast function. These two aims will be pursued during the final postdoctoral training period of the K99 phase. Aim 3 seeks to identify how HIV-exposed mitochondria reprogram trophoblast biology, impairing placental function and affecting fetal development in vivo. This third aim will be pursued during the R00 phase of the project. Successful completion of these aims will provide new insights into the mechanisms underlying HIV infection, identifying potential therapeutic targets to mitigate vertical transmission and placental pathologies caused by HIV and other viruses. During the mentored phase, the PI will gain expertise in primary cell culture, metabolomics, trophoblast organoids, and mitochondrial epigenetics to examine how HIV infects the placenta and disrupts cellular metabolism—establishing a foundation for the R00 phase. With guidance from the advisory team, this training and research will contribute to the identification of therapeutic strategies to improve outcomes for infants and individuals with HIV, while positioning the investigator to establish an independent, competitive R01-funded laboratory at the intersection of HIV, TNTs, placental biology, and mitochondria.

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Determinants of Vaccine Responses in Low-Income Countries (LICs)

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National Institute of Allergy and Infectious Diseases (NIAID)

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By mentoring junior investigators from the United States and low-come countries (LICs) in patient- oriented research (POR) in global health, particularly in vaccine-preventable diseases, I hope to build local capacity, improve outcomes and reduce health disparities. Working within the resource-limited health systems in LICs is challenging, and the influences of co-infections (particularly parasitic infections), anemia, undernutrition, and various microorganisms on vaccine efficacy may be underappreciated. For these reasons, vaccines and vaccine campaigns developed for and assessed in high-income countries (HICs) cannot be assumed to be feasibly implemented or to perform similarly in LICs. For instance, SARS-CoV-2 vaccination with mRNA-based vaccines in sub-Saharan Africa has been limited by the cold-chain requirement of these vaccines. Cultural and socio-economic factors have led Malawians to generally choose receiving the single dose Ad26.COV2-S rather than the ChAdOx1 vaccine. Growing evidence suggests that performance of vaccines in LICs is lower than HICs and the protective immunity elicited by some vaccines is shorter than originally anticipated. In an interconnected world where diseases do not have borders, optimizing interventions to control transmittable diseases in LICs impacts the health of populations worldwide.  The overall goal is to train junior investigators across disciplines to optimize vaccinations in Malawi, a sub-Saharan African country in which I have established a thriving research infrastructure. The first two aims of this application, supported by my R01AI164686-funded project, will assess i) the longevity of antibodies (magnitude and function) and memory cells induced by the Ad26.COV2-S SARS-CoV-2 vaccine; ii) the contribution of pre-existing changes in innate immunity to these responses; iii) the association of malaria, micronutrient deficiency, and microorganisms colonizing the nasopharynx with these responses. In the third aim, funded through this proposal, we will address the longevity of five childhood vaccines, focusing particularly on optimizing the timing of re-vaccination. The importance of this question became obvious in 2023 when three poliovirus cases were identified in Malawi. The Ministry of Health, with no relevant data available, decided to revaccinate all children with an arbitrary cutoff of 15 years of age.  I have mentored several investigators in POR, particularly from Malawi, and have been conducting research in the immunoepidemiology of vaccines in LICs (including Malawi) since 2015. With this award, I would be able to expand my panel of trainees, devote more time to each of them, acquire training to further my mentorship skills as well as my own professional skillset, and expand the focus of the research to include other childhood vaccines. With the research infrastructure built in Malawi, I am now well-equipped to successfully train clinician scientists and other junior investigators in POR in infectious diseases, particularly in vaccines in LICS.

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Mid-Career Clinical Scientist Award (K24)

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Understanding Ribosomal Dependent Virulence Pathways Employed by Non-Structural Protein 1 in Emerging Human Beta-Coronaviruses

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National Institute of Allergy and Infectious Diseases (NIAID)

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Project Summary/ Abstract Betacoronaviruses (β-CoVs) present a substantial threat to global health. Hence, determining viral targets for therapeutic intervention is an utmost priority. One attractive target is Non-structural protein 1 (Nsp1) which restricts the innate immune response by inhibiting host gene expression. Nsp1 is encoded by all β-CoVs and is hypothesized to function through three host-viral interaction pathways: two are in the cytosol requiring the ribosome, and one in the nucleus impeding host mRNA trafficking through the nuclear pore. First in the cytosol, Nsp1 restricts protein translation by binding inside the mRNA entry channel of the ribosome, sterically blocking proper host mRNA loading. Secondly, Nsp1 coordinates endonuclease cleavage of host mRNA using eukaryotic initiation factor 3g (eIF3g) as a co-factor on the ribosome. This cleaves host mRNA at the 5’ end leaving the transcripts translationally inert. However, for Middle East Respiratory Virus (MERS), I present data showing the eIF3g alone is not sufficient as a co-factor for endonuclease cleavage. Recent evidence has emerged emphasizing the importance of the two ribosome-dependent mechanisms for Nsp1 function and viral replication. However, the endonuclease function of Nsp1 remains poorly understood. I hypothesize that the endonuclease function is a crucial aspect of Nsp1 biology and elucidating its molecular mechanism will pave the way for potent drug development which can restrict current and future β-CoVs. Currently, the FDA approved drug, Montelukast, has been shown to inhibit the SARS-CoV-2 endonuclease complex. Aim 1: Determine the structure of the SARS-CoV-2 Nsp1 endonuclease complex. I present a preliminary cryoEM structure of SARS-CoV-2 Nsp1 facilitating the endonuclease complex. I show Nsp1 binding eIF3g and mRNA on 40S subunit of the ribosome, however, my study was limited in scale and is currently at low resolution (~6Å local resolution). As such I propose collecting a large dataset on a 300kV microscope to obtain a high-resolution map, resolving the molecular details of the endonuclease function. Additionally, I propose binding studies to elucidate details of the mechanism of action for Montelukast inhibiting the endonuclease complex of SARS-CoV-2 Nsp1. Successful completion of this aim will determine the molecular mechanism of the endonuclease function of Nsp1 and significantly advance Nsp1 as a therapeutic target. Aim 2: Elucidate essential co-factors for MERS Nsp1 endonuclease function. My preliminary data strongly supports that eIF3g alone is not sufficient as a co-factor for MERS Nsp1 endonuclease function. Thus, I will employ proximity labeling with TurboID to identify what co-factors are needed for MERS Nsp1 to cleave mRNA by employing biochemical and molecular biology methods. Then I will recapitulate the minimal endonuclease complex for MERS Nsp1 in-vitro. Successful completion of this aim will show how the endonuclease function of Nsp1 is conserved across the divergent landscape of β-CoVs.

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Middle East Respiratory Syndrome Coronavirus

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BREATHE WELL: Development and Implementation of a Training Program to Increase Vaccination in Early Childcare and Education Centers

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National Center for Immunization and Respiratory Diseases (NCIRD)

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/ ABSTRACT Early childcare and education (ECE) centers are trusted institutions that engage with parents regularly, positioning them as key messengers for childhood immunization and respiratory health promotion. While ECE centers ensure compliance with mandated vaccines, their potential to support uptake of non-mandated immunizations—such as influenza vaccine, COVID-19 vaccine, maternal RSV vaccine, and nirsevimab antibody—remains underutilized. The BREATHE Well (Building Readiness, Engagement, and Trust for Healthy Environments) Toolkit is an evidence-based intervention designed to enhance ECE-originating vaccine communication, training ECE staff to effectively engage parents on immunization topics. This study will evaluate the feasibility, acceptability, and effectiveness of the BREATHE Well toolkit using a cluster- randomized controlled trial (RCT). The project will be guided by three specific aims: (1) Develop and refine the BREATHE Well toolkit through formative research, incorporating input from ECE staff, parents, and public health officials; (2) Assess the acceptability and feasibility of the toolkit through focus groups and surveys with ECE staff and parents in demonstration sites within Michigan; and (3) Evaluate the effectiveness of the toolkit in a cluster-randomized trial of ECE centers, measuring changes in parental vaccine confidence, intent to vaccinate, and staff capacity to serve as trusted messengers. The BREATHE Well toolkit will be designed as a scalable approach usable in different types of ECEs. Findings from this study will inform best practices for integrating vaccine-related education into ECE settings, with the goal of increasing parental vaccine confidence and improving uptake of recommended immunizations.

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Thyroid hormone mediated reprogramming of the basolateral amygdala by adolescent social deprivation

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Social disconnection in humans, particularly during adolescence, is associated with substance use disorder vulnerability. In mice, adolescent social isolation profoundly alters reward processing in adulthood; increasing the preference for drugs of abuse, enhancing associative learning, altering dopaminergic signaling and transcription within the BLA and extended reward circuitry. Intriguingly, these phenomena are all also associated with thyroid hormone signaling. Further, dysregulation of thyroid hormone in early life is associated lifetime risk for reward-related mood disorders and altered development of monoaminergic systems. In adults, thyroid hormone dysregulation is associated with substance- and alcohol use disorders. Therefore, we propose that the persistent impacts of adolescent social isolation result from transient dysregulation of thyroid hormone signaling during the sensitive period of adolescence. Thyroid hormones, when bound to their receptors, are transcription factors that mediate various epigenetic processes and regulate gene expression. Aberrant thyroid hormone signaling at critical developmental periods persistently alters transcription in other tissues through epigenetic reprogramming of thyroid hormone sensitive genes. Despite its critical role in neurodevelopment and its link to substance use disorder, the consequences of thyroid hormone dysregulation in adolescence, a key period for reward circuitry development and substance use disorder vulnerability, is virtually unknown. Our preliminary data suggest that circulating thyroid hormones and expression of its receptors are transiently disrupted in adolescence by social isolation and this is associated with enhanced expression of GABAergic neuronal markers in the adult basolateral amygdala (BLA), a key reward-related brain region  Here, we will test the hypothesis that thyroid hormone is critical for development of the basolateral amygdala (BLA) during adolescence and that isolation-induced disruptions to the thyroid hormone system result in lasting epigenetic reprogramming of the reward circuitry to increase cocaine sensitivity. First, we will determine how adolescent social isolation impacts thyroid hormone-mediated transcription in the BLA (Aim 1). Then we will determine if thyroid hormone dysregulation induced by adolescent isolation disrupts cell-type specific transcriptional profiles within the BLA (Aim 2). Finally, we will disrupt thyroid hormone receptor beta levels specifically during adolescence to determine its role in reward-related behavior in (Aim 3). Together, these foundational studies will establish a role for thyroid hormone-mediated programming of the BLA and uncover novel mechanisms of isolation-induced reprogramming of SUD vulnerability during adolescence - an endpoint that has become even more urgent given the known reductions in social interactions due to the mitigation of Covid-19 for the current generation of adolescents.

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Cleavage Under Targets and Release Using Nuclease

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AT191: An inhaled & precision RNA therapeutic with pan-variant SARS-CoV-2 efficacy

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National Institute of Allergy and Infectious Diseases (NIAID)

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This Phase II SBIR will de-risk a new class of antivirals that can be developed to target any RNA virus from SARS-CoV-2 to influenza. The effort will specifically translate a lead, platform-derived SARS-CoV-2 candidate (AT191) designed to be self-administered and to prevent hospitalizations or deaths by any SARS-CoV-2 variant. Despite vaccines and 2 blockbuster antivirals marketed to prevent hospitalizations, 900,000 Americans were hospitalized due to SARS-CoV-2 in 2023. Beyond vaccine hesitancy and durability concerns, existing antivirals only reduce hospitalizations and deaths by 40–50%. SARS-CoV-2 antivirals are further limited by contraindications (e.g. Paxlovid) and safety concerns (e.g. molnupiravir). Moreover, there is a risk that SARS- CoV-2 acquires resistance to all existing classes of antivirals—as occurred with all SARS-COV-2 monoclonal antibodies prior to 2024. There is a clear unmet need for new classes of antivirals, especially antivirals that can: (i) be used at-home to prevent hospitalizations, and (ii) maintain (variant-proof) efficacy as novel variants emerge. Encrypted RNA (encRNA) is a new class of RNA developed by Autonomous Therapeutics. The plug-and-play platform technology can develop antivirals against any RNA virus and can encode any therapeutic protein. Unlike state-of-the-art mRNA, each platform-derived encRNA only activates its (broad-spectrum) antiviral payload in targeted virus-infected cells. More specifically, encRNA only translate encoded proteins when bound, transcribed, and amplified by targeted viral RNA polymerase (RdRp) complexes conserved across a viral species. Thus, encRNA remain translationally inactive and safe in uninfected cells (e.g. as prophylactics). AT191 is our lead, first-in-class encRNA therapeutic candidate developed to confer inhaled and variant-proof efficacy against all variants of SARS-CoV-2 (and SARS-CoV-1). AT191 confers precision and pan-sarbecovirus efficacy—because AT191’s antiviral payload (IFN-β) is only activated and translated by sarbecovirus RdRp. In Phase I-equivalent studies, we developed: (i) the encRNA platform technology, (ii) the AT191 lead candidate, and (iii) an inhalable lipid nanoparticle (LNP) for encRNA self-administration using marketed nebulizers. We further demonstrated the (iv) variant-proof efficacy of AT191 against every tested SARS-CoV-2 variant in vitro, and the (v) preliminary in vivo safety and efficacy of AT191 in both mice and hamsters. Here we propose to develop AT191 into a GLP-ready candidate ready for IND-enabling studies. We propose to test the pan-sarbecovirus efficacy (SARS-CoV-1 & 2) of AT191 in vivo and to perform critical CMC, inhalation, dose-timing, and dose-finding studies in hamsters. We will also test safety/efficacy in non-human primates. The effort will culminate in a pre-IND. If successful in follow-on clinical studies, AT191 could be used at-home as a prophylactic or therapeutic: e.g. for immediate use after exposure to an infected child or family member. Beyond SARS-CoV-2, the same encRNA-LNP platform technology could be used to develop precision and variant-proof candidates for any RNA virus—including viruses for which no safe and effective antivirals exist.

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Small Business Innovation Research Grant

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United States National Institutes of Health

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Targeting NINJ1-mediated Plasma Membrane Rupture to Prevent Thrombosis

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National Heart Lung and Blood Institute (NHLBI)

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This proposal focuses on investigating the role of plasma membrane rupture (PMR) of pyroptotic macrophages in thrombosis and examine the potential therapeutic approaches targeting pyroptosis and PMR. Thrombotic complications remain a leading cause of morbidity and mortality worldwide. Current antithrombotic therapies target platelets and the coagulation cascade, common pathways for normal blood clotting upon injury (hemostasis) and the pathological formation of blood clot (thrombosis). These treatments often carry bleeding risks by disrupting hemostasis and do not address the inﬂammatory roots of thrombosis. Inﬂammation- dependent blood clotting is part of the body's response to pathogens, but excessive inﬂammation can result in thrombosis. Emerging research underscores inﬂammation's pivotal role in thrombosis across various conditions, including heart disease, deep vein thrombosis, sepsis, and COVID-19. Targeting PMR offers a strategy to simultaneously manage inﬂammation and thrombosis while preserving normal clotting mechanisms. Pyroptosis, a lytic form of cell death in monocytes/macrophages triggered by inﬂammasomes, is crucial in responding to bacterial infection and sterile inﬂammation, with PMR being a terminal event in this process. Our previous research has identiﬁed macrophage pyroptosis as a key contributor to thrombosis, through the release of microvesicles containing tissue factor (a key initiator of the coagulation cascade together with factor VII/VIIa). This mechanism is linked to PMR, highlighting PMR as a potential trigger of thrombosis and as a desirable inﬂammatory target. Because it is the ﬁnal step in a chain of inﬂammatory processes, targeting PMR may carry low risk of immunosuppression. NINJ1, initially identiﬁed in nerve injury, emerges as the executioner of PMR that was previously thought to be passive and uncontrollable. This discovery unveils a potential new target for thrombosis intervention. Our preliminary studies showed reduced NINJ1 expression decreased thrombosis and the release of pyroptotic microvesicles. This research aims to investigate the role of myeloid NINJ1 in thrombosis, the mechanisms behind the release of pyroptotic microvesicles, and the feasibility of targeting pyroptosis and NINJ1-mediated PMR for thrombosis prevention. The expected results will enhance our understanding of NINJ1-mediated PMR in immune cell-induced thrombosis, potentially leading to targeted treatments for thrombosis-related conditions like heart disease, venous thromboembolism, cancer, and infectious disease.

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Spatial and Temporal Adjuvant Delivery for Skin mRNA Vaccination

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National Institute of Allergy and Infectious Diseases (NIAID)

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The success of COVID-19 mRNA vaccines has showcased the effectiveness of this technology in rapid design, manufacturing, and adaptation to emerging viral threats. However, several imitations remain, including their instability requiring cold-chain storage that limits their global distribution, the necessity for two doses for optimal efficacy, limited immunity to closely matched viral strains, and quick-waning immunity following the initial two doses. These limitations can be potentially addressed by potent adjuvants. However, traditional adjuvants, co-delivered with vaccines to enhance antigen-presenting cell (APC) recruitment and functionality, are unsuitable for mRNA vaccines, because the co-delivered adjuvant provokes innate immune responses that interfere with mRNA translation, reducing its immunogenicity. Our recent investigation demonstrated that mRNA vaccines, particularly when delivered intradermally, could be substantially augmented by adjuvant delivery at different times and locations relative to mRNA vaccination, effectively circumventing the interference with mRNA transcription and translation. The current proposal aims to determine whether intranasal (IN) or intradermal (ID) delivery of a newly developed adjuvant can expand the breadth and longevity of trivalent influenza (flu) mRNA vaccine administered via a microneedle array patch (MNP). Specifically, we will construct a trivalent self-amplifying mRNA (saRNA) flu vaccine, encapsulated within liposomes free of cationic or ionizable lipids using our proprietary technology, and then loaded into our caved MNP after lyophilization. The antigen expression, immunogenicity, and efficacy of this saRNA flu vaccine will be optimized and evaluated in mice. Aim 2 will define the optimal time window of IN or ID adjuvant delivery following MNP-saRNA- flu immunization. Antigens-specific T-cell responses and broad neutralization antibodies across homosubtypic and heterosubtypic flu strains will be assessed and compared with or without the adjuvant and between IN and ID adjuvant delivery. The longevity of the specific immune responses will be also monitored over several months. Aim 3 will validate the efficacy of MNP immunization, alongside delayed adjuvant delivery, against various flu viruses in young and aging mice. If successful, the innovative strategy can be extended to other respiratory viral vaccines, such as those for COVID-19, respiratory syncytial viruses, etc., broadening the breadth and efficacy of various RNA-based vaccines delivered parenterally.