Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Pekarek, Matthew J.; Petro-Turnquist, Erika; Rubrum, Adam; Webby, Richard J.; Weaver, Eric A.

doi:10.3390/v14061299

Cited by 4 publications

(2 citation statements)

References 47 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The adapted viruses were collected from the final passage of mouse lungs, grown in SPF embryonated chicken eggs, and prepared and quantified as specified above. The HA gene of B/Phuket/3073/2013 and B/Florida/04/2006 were sequenced as previously described [ 30 ] to ensure no mutations had occurred during serial lung passaging.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice

Petro-Turnquist,

Corder Kampfe,

Gadeken

et al. 2024

Pathogens

Self Cite

View full text Add to dashboard Cite

Influenza B virus is a respiratory pathogen that contributes to seasonal epidemics, accounts for approximately 25% of global influenza infections, and can induce severe disease in young children. While vaccination is the most commonly used method of preventing influenza infections, current vaccines only induce strain-specific responses and have suboptimal efficacy when mismatched from circulating strains. Further, two influenza B virus lineages have been described, B/Yamagata-like and B/Victoria-like, and the limited cross-reactivity between the two lineages provides an additional barrier in developing a universal influenza B virus vaccine. Here, we report a novel multivalent vaccine using computationally designed Epigraph hemagglutinin proteins targeting both the B/Yamagata-like and B/Victoria-like lineages. When compared to the quadrivalent commercial vaccine, the Epigraph vaccine demonstrated increased breadth of neutralizing antibody and T cell responses. After lethal heterologous influenza B virus challenge, mice immunized with the Epigraph vaccine were completely protected against both weight loss and mortality. The superior cross-reactive immunity conferred by the Epigraph vaccine immunogens supports their continued investigation as a universal influenza B virus vaccine.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Immunizations, bleeds, and experimental infections were performed under isoflurane or ketamine and xylazine-induced anesthesia. [30] to ensure no mutations had occurred during serial lung passaging.…”

Section: Ethics Statementmentioning

confidence: 99%

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice

Petro-Turnquist,

Corder Kampfe,

Gadeken

et al. 2024

Pathogens

Self Cite

View full text Add to dashboard Cite

show abstract

A Universal, Single-Component Multilayered Self-Assembling Protein Nanoparticle Vaccine Based on Extracellular Domains of Matrix Protein 2 Against Both Influenza A and B

Zhang,

Gomes,

Lee

et al. 2024

Preprint

View full text Add to dashboard Cite

The development of an effective and broadly protective influenza vaccine against circulating and emerging strains remains elusive. In this study, we evaluated single-component self-assembling protein nanoparticles (1c-SApNPs) presenting the conserved matrix protein 2 ectodomain (M2e) from influenza A and B viruses (IAV and IBV, respectively) as a universal influenza vaccine. We previously designed a tandem antigen comprising three IAV M2e domains of human, avian/swine, and human/swine origins (termed M2ex3). The M2ex3-presenting 1c-SApNPs conferred complete protection in mice against sequential lethal challenges with H1N1 and H3N2. To broaden this protection to counter IBVs, we designed a series of antigens incorporating different arrangements of three IAV M2e domains and three copies of IBV M2e. The tandem repeats of IAV and IBV (termed influenza A-B) M2e arrayed on the I3-01v9a 60-mer 1c-SApNP, when formulated with an oil-in-water emulsion adjuvant, generated greater M2e-specifc immunogenicity and protective efficacy than the soluble influenza A-B M2e trimer, as indicated by higher survival rates and lower weight loss post-challenge. Importantly, one of the influenza A-B M2e SApNP constructs elicited 100% protection against a lethal influenza A (H1N1) challenge in mice and 70% protection against a lethal influenza B (Yamagata lineage) challenge, the latter of which has not been reported in the literature to date. Our study thus provides a truly universal single-component M2e-based vaccine candidate against two major types of influenza virus circulating in humans.

show abstract

Impact of adjuvant: Trivalent vaccine with quadrivalent-like protection against heterologous Yamagata-lineage influenza B virus

Myers

Gallagher²,

Woolfork³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

As new vaccine technologies and platforms, such as nanoparticles and novel adjuvants, are developed to aid in the establishment of a universal influenza vaccine, studying traditional influenza split/subunit vaccines should not be overlooked. Commercially available vaccines are typically studied in terms of influenza A H1 and H3 viruses but influenza B viruses need to be examined as well. Thus, there is a need to both understand the limitations of split/subunit vaccines and develop strategies to overcome those limitations, particularly their ability to elicit cross-reactive antibodies to the co-circulating Victoria (B-V) and Yamagata (B-Y) lineages of human influenza B viruses. In this study, we compared three commercial influenza hemagglutinin (HA) split/subunit vaccines, one quadrivalent (H1, H3, B-V, B-Y HAs) and two trivalent (H1, H3, B-V HAs), to characterize potential differences in their antibody responses and protection against a B-Y challenge. We found that the trivalent adjuvanted vaccine Fluad, formulated without B-Y HA, was able to produce antibodies to B-Y (cross-lineage) on a similar level to those elicited from a quadrivalent vaccine (Flucelvax) containing both B-V and B-Y HAs. Interestingly, Fluad protected mice from a lethal cross-lineage B-Y viral challenge, while another trivalent vaccine, Fluzone HD, failed to elicit antibodies or full protection following challenge. Fluad immunization also diminished viral burden in the lungs compared to Fluzone and saline groups. The success of a trivalent vaccine to provide protection from a cross-lineage influenza B challenge, similar to a quadrivalent vaccine, suggests that further analysis of different split/subunit vaccine formulations could identify mechanisms for vaccines to target antigenically different viruses. Understanding how to increase the breadth of the immune response following immunization will be needed for universal influenza vaccine development.

show abstract

Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Cited by 4 publications

References 47 publications

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice

A Universal, Single-Component Multilayered Self-Assembling Protein Nanoparticle Vaccine Based on Extracellular Domains of Matrix Protein 2 Against Both Influenza A and B

Impact of adjuvant: Trivalent vaccine with quadrivalent-like protection against heterologous Yamagata-lineage influenza B virus

Contact Info

Product

Resources

About