Biology subjects

Myers, M. L.

Publications and source records attributed to Myers, M. L..

4 recordsLinked to original sources

bioRxiv2024

Structure-guided assembly of an influenza spike nanobicelle vaccine provides pan H1 intranasal protection

Development of intranasal vaccines for respiratory viruses has gained popularity. However, currently only a live-attenuated influenza vaccine is FDA-approved for intranasal administration. Here, we focused on influenza virus as it circulates seasonally, has pandemic potential, and has vaccine formulations that present hemagglutinin (HA) in different structural arrangements. These display differences have not been correlated with induction of pan-H1 antibodies or shown to provide intranasal protection. Using electron microscopy, biochemistry and animal studies, we identified HA complexes arranged as lipid discs with multiple trimeric HAs displayed along the perimeter, termed spike nanobicelles (SNB). We utilized a structure-guided approach to synthesize in vitro assembled spiked nanobicelles (IA-SNB) from a classical 1934 H1N1 influenza virus. IA-SNBs elicited pan-H1 antibodies and provided protection against antigenically divergent H1N1 viruses via intranasal immunizations. Viral glycoprotein spikes displayed as SNBs could aid in combating antigenic variation and provide innovative intranasal vaccines to aid universal influenza vaccine development.

microbiology↗

bioRxiv2024

Analysis of polyclonal and monoclonal antibody to the influenza virus nucleoprotein in different oligomeric states

Influenza virus nucleoprotein (NP) is one of the most conserved influenza proteins. Both NP antigen and anti-NP antibodies are used as reagents in influenza diagnostic kits, with applications in both clinical practice, and influenza zoonotic surveillance programs. Despite this, studies on the biochemical basis of NP diagnostic serology and NP epitopes are not as developed as for hemagglutinin (HA), the fast-evolving antigen which has been the critical component of current influenza vaccines. Here, we characterized the NP serology of mice, ferret, and human sera and the immunogenic effects of NP antigen presented as different structural complexes. Furthermore, we show that a classical anti-NP mouse mAb HB65 could detect NP in some commercial influenza vaccines. MAb HB65 bound a linear epitope with nanomolar affinity. Our analysis suggests that linear NP epitopes paired with their corresponding characterized detection antibodies could aid in designing and improving diagnostic technologies for influenza virus.

microbiology↗

bioRxiv2022

Commercial influenza vaccines vary in both the structural arrangements of HA complexes and in induction of antibodies to cross-reactive HA epitopes

Influenza virus infects millions of people annually and can cause global pandemics. Hemagglutinin (HA) is the primary component of commercial influenza vaccines (CIV), and antibody to HA is a primary correlate of protection. Persistent antigenic variation of HA requires that CIV be reformulated for new strains yearly. Differences in structural organization of HA has not been correlated with induction of broadly reactive antibodies, and CIV formulations can vary in how HA is organized. Using electron microscopy to study four current CIV, we found that these different formulations contained a variety of structures including: individual HAs, starfish-like structures with up to 12 HA molecules, and novel "spiked nanodisc" structures that displayed over 50 HA molecules along the complexs perimeter. These spiked nanodiscs uniquely exposed conserved stem epitopes and elicited the highest levels of heterosubtypic cross-reactive antibodies. Overall, we found that HA structural organization can be an important CIV parameter and can be associated with the induction of cross-reactive antibodies to conserved HA epitopes.

microbiology↗

bioRxiv2019

Designed Nanoparticles Elicit Cross-Reactive Antibody Responses To Conserved Influenza Virus Hemagglutinin Stem Epitopes

Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that an alpha-helical fragment (helix-A) from the conserved stem region can be displayed on nanoparticles. The stem region of HA on these nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, H1-nanoparticles protected mice from lethal challenge with H1N1 influenza virus. Importantly, antibodies elicited by these nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity. The helix-A stem nanoparticle design represents a novel approach to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens up opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.\n\nSignificanceInfluenza virus is a public health issue that affects millions of people globally each year. Commercial influenza vaccines are based on the hemagglutinin (HA) surface glycoprotein, which can change antigenically every year, demanding the manufacture of newly matched vaccines annually. HA stem epitopes have a higher degree of conservation than HA molecules contained in conventional vaccine formulations and we demonstrate that we are able to design nanoparticles that display hundreds of HA stem fragments on nanoparticles. These designed nanoparticles are heat-stable, elicit antibodies to the HA stem, confer protection in mouse challenge models, and show cross-reactivity between HA subtypes. This technology provides promising opportunities to improve seasonal vaccines, develop pandemic preparedness vaccines, and facilitate the development of a universal influenza vaccine.

microbiology↗