Biology subjects

Wymore Brand, M.

Publications and source records attributed to Wymore Brand, M..

3 recordsLinked to original sources

bioRxiv2026

A multivalent mRNA-lipid nanoparticle vaccine containing eight hemagglutinin antigens elicited broad neutralizing antibody responses and protected against influenza A virus challenge in swine.

The diversity within H1 and H3 subtype influenza A viruses (IAV) in swine prevents effective vaccine control approaches with inactivated whole-virus vaccines. We addressed the challenge of controlling co-circulating hemagglutinin (HA) clades of swine IAV with the development of a multivalent mRNA-lipid nanoparticle (LNP) vaccine expressing 8 HA proteins to maximize genetic coverage. We applied a computational approach to select eight HA genes that represented 95% of the observed IAV detected in the United States between 2022 and 2025. Piglets were vaccinated and boosted intramuscularly with either individual HA mRNA-LNP or an 8-HA multivalent mRNA-LNP. Serum was collected to evaluate systemic antibody levels. Twenty-one days post-boost, pigs were challenged with a field relevant H1 1A.3.3.3-c3 IAV strain. The 8-HA multivalent mRNA-LNP vaccine induced neutralizing antibodies against all eight antigens and vaccinees were protected against lung lesions, with lesion scores similar to non-challenged animals. Homologous monovalent vaccination significantly reduced IAV detection in nasal secretions and in the lungs. Heterologous monovalent vaccination was not cross-protective but did not induce vaccine-associated enhanced respiratory disease. We provide evidence that monovalent and multivalent mRNA-LNP influenza vaccines elicited neutralizing antibody responses in pigs and protected against viral challenge. The versatility and capacity for rapidly updating the mRNA-LNP vaccine platform make it an appealing tool to improve animal health and minimize the circulation and diversity of IAV in swine. ImportanceInfluenza A virus is an important respiratory pathogen in swine, and zoonotic transmission of swine strains to humans remains a public health risk. Control strategies against IAV in swine herds rely heavily on biosecurity measures and vaccination. However, the antigenic diversity of IAV circulating in swine challenges current vaccination programs, and there is a need for broadly protective vaccines or platforms that can rapidly update components to reflect circulating diversity. mRNA-LNP vaccines have emerged as promising vaccine platforms, offering simultaneous delivery of multiple antigens, rapid development, scalable manufacturing, and potent immunogenicity. In this study, we assessed the immunogenicity and protective capacity of monovalent and multivalent mRNA-LNP vaccines encoding eight representative IAV HA antigens. To our knowledge, this is the first study to objectively select multiple representative endemic swine IAV strains by quantifying genetic diversity within the phylogeny and to apply this selection to rationally design and evaluate a multivalent HA mRNA-based influenza vaccine in the swine model.

microbiology↗

bioRxiv2025

Impact of Maternal Antibodies and Weaning Stress on the Replication and Transmission of Human H3N2 Influenza A in Piglets

Modern swine production facilitates indoor respiratory contact between human employees and pigs in their care, creating conditions for interspecies transmission of influenza A virus (IAV). Sow vaccination is routinely practiced in the U.S. to transfer maternal derived antibodies (MDA) to piglets. Weaning is a highly stressful period for piglets that requires increased human interaction. This study investigates the effect of maternal antibodies on the susceptibility of weaned piglets to a human-origin H3N2 IAV. Weaned piglets often possess mixed immunity from MDA, which may be antigenically matched or mismatched to circulating viruses. Given the repeated spillover of human seasonal H3N2 into swine, we specifically examined how matched and mismatched MDA, acquired from vaccinated sows, influenced piglet susceptibility. Additionally, we assessed the impact of weaning-related stress on the outcome of viral challenge. The H3N2 virus was generated by reverse genetics to mimic the 2010.1 H3N2 introduction from humans to swine. Challenged seeder piglets were divided by immune and weaning status. Two days post inoculation, naive direct contact pigs were placed with seeders. IAV qRT-PCR and virus titration were performed on nasal swabs and bronchoalveolar lavage fluid to evaluate shedding and transmission kinetics. Matched MDA were effective in reducing shedding in challenged pigs and minimizing transmission to contacts. There was an increase in shedding and transmission in weaned pigs compared to littermates that remained on the sow. These results identify critical control points in production where changing practices could mitigate human-to-swine and swine-to-swine transmission to prevent establishment of novel lineages in pig populations. ImportanceDefining the factors that increase the susceptibility of pigs to infection with human influenza A viruses (IAV) is critical to understand why those viruses transmit to the new host. IAV is frequently detected in nursing pigs, where it was shown that maternal derived antibodies (MDA) may reduce clinical signs but may not prevent infection and transmission. Infected weaned piglets can then move viruses from the sow farm to offsite nurseries, where they can cause outbreaks with clinical disease as MDA wanes. Determining management practices that can be modified to reduce interspecies transmission of viruses to pigs is economically beneficial to the swine industry and could help define measures to prevent new spillover events. Reducing spillover of human IAV into pig populations also benefits public health by reducing genomic and phenotypic diversity in swine and the subsequent potential for zoonotic transmission.

immunology↗

bioRxiv2025

United States PRRSV 1-4-4 L1C.5 isolate demonstrates similar pathogenicity to a historic Chinese highly pathogenic PRRSV

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economic and animal health burden on the United States swine industry due to morbidity- and mortality-associated losses affecting all stages of pig production. Currently, a large proportion of losses are attributed to a highly virulent PRRSV strain, PRRSV 1-4-4 L1C.5. To benchmark the virulence of PRRSV 1-4-4 L1C.5, a study was conducted to compare pathogenicity of this contemporary strain to a historical Chinese highly pathogenic PRRSV (HP-PRRSV) strain, JXwn06, that devastated the Chinese and other Asian swine industries since 2006, as well as a moderately virulent United States PRRSV strain, MN184, considered to be one of the most virulent PRRSV strains circulating in the United States in the early 2000s. Weaned pigs were inoculated with PRRSV strains L1C.5, JXwn06, MN184, or mock inoculum and necropsied at 2, 6, and 10 days post inoculation, or as needed due to severe disease. Clinical metrics, viral loads, cytokine concentrations, PRRSV-specific antibody concentrations, and pathology were compared between treatment groups to compare pathogenicity. Results indicate a high degree of similarity disease dynamics between L1C.5 and JXwn06 animals that diverged from MN184 and mock animals. Findings indicate L1C.5 and JXwn06 cause more severe morbidity and mortality in weaned pigs than MN184. Results may be applied to develop more effective strategies for mitigating PRRSV 1-4-4 L1C.5 outbreaks currently plaguing the United States swine industry.

microbiology↗