# Mechanism of membrane inactivation method to prepare enveloped virus vaccines

> **NIH NIH R21** · CORNELL UNIVERSITY · 2021 · $248,896

## Abstract

Project Summary / Abstract
The World Health Organization’s list of priority pathogens that pose the highest public health risks, and for which
there are insufficient treatments, is composed solely of enveloped viruses. Examples of enveloped viruses highly
relevant to human health are: HIV, influenza A viruses (IAV), EboV, MERS-CoV, SARS, SARS-CoV-2, CHIKV,
NiV, HeV, RSV, ZIKV, and the influenza A (IAV) and B (IBV) viruses. The human cost of their illnesses is in the
millions, and the economic cost is in the hundreds of billions of dollars per year. The standard methods for
generating vaccines, including whole inactivated virus (WIV), live attenuated virus (LAV), sub-unit, and
DNA/RNA, often fail to result in effective prophylaxis. WIV vaccines have some advantages such as their safety
and their presentation of multiple antigens to the immune system. However, WIVs often induce insufficient
immunity or even vaccine-enhanced disease due to antigen conformational differences between the WIV vaccine
and the challenge virus. Our proposal addresses the pressing need for more effective and broadly applicable
WIV vaccines by exploring a promising new technology using the antiviral XM-01 (patent applications pending).
Current virus inactivation methods for WIV preparation use chemical or physical means that often damage or
modify viral antigens, including the glycoproteins, which are important immunogens for the enveloped viruses.
This often leads to non-protective or even destructive immune responses. For example, the efficacies of the
currently used WIV vaccines for IAV are between 10%-60%. We recently developed a novel vaccine platform
that uses XM-01 to target the viral membrane while largely preserving the native conformation of viral
glycoproteins. Preliminary data using IAV as a model indicates that immunization with XM-01-inactivated IAV
particles improved induction of neutralizing antibodies to both hemagglutinin (HA) and neuraminidase (NA), as
well as animal survival, compared to the traditional formalin-inactivated IAV particles. As XM-01 is a broad-
spectrum inhibitor of enveloped viruses, our central hypothesis is that virus inactivation with XM-01 improves
WIV vaccine development by preserving glycoprotein conformations, facilitating the effective generation of a
protective immune response. We will test our hypothesis with two Specific Aims:
Aim 1: Determine the mechanism by which XM-01 inactivated virus affords improved immune responses
as compared to traditional WIV vaccine methods, using the influenza virus model.
Aim 2: Determine XM-01 vaccination safety, efficacy, and breadth of immune responses.
We expect this work will improve our understanding of the mechanism by which XM-01 membrane-mediated
viral inactivation generates an enhanced protective immune response, and to assess the new method’s safety,
efficacy, and ability to generate broadly protective antibodies against heterologous viral strains, overall assessing
whether this new mod...

## Key facts

- **NIH application ID:** 10309175
- **Project number:** 1R21AI156731-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Hector Aguilar-Carreno
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $248,896
- **Award type:** 1
- **Project period:** 2021-06-23 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10309175

## Citation

> US National Institutes of Health, RePORTER application 10309175, Mechanism of membrane inactivation method to prepare enveloped virus vaccines (1R21AI156731-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10309175. Licensed CC0.

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