| Autor: |
Luo, Zhaochen, Miranda, Hector A., Burke, Kaitlyn N., Spurrier, M. Ariel, Berry, Madison, Stover, Erica L., Spreng, Rachel L., Waitt, Greg, Soderblom, Erik J., Macintyre, Andrew N., Wiehe, Kevin, Heaton, Nicholas S. |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 5/1/2024, Vol. 16 Issue 745, p1-15, 15p |
| Abstrakt: |
Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine–mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein. Vaccine-induced antibodies were disproportionally redistributed to the more conserved stalk of the HA without hindering, and in some cases improving, antibody responses against the head domain. These improved responses led to increased protection against homologous and heterologous viral challenges in both mice and ferrets compared with conventional vaccine approaches. Thus, antigenically complex protein mixtures can at least partially overcome HA head domain antigenic immunodominance and may represent a step toward a more universal influenza vaccine. Editor's summary: A major goal for next-generation influenza vaccines is to elicit antibody responses to more conserved regions, such as the hemagglutinin (HA) stalk. To accomplish this, Luo et al. used a mutagenesis approach to generate a mixture of recombinant HAs that could be used as a vaccine. The mutations were limited to the immunodominant Sb site of the HA head, which the authors hypothesized would push the antibody response to favor immunosubdominant domains. The authors found that vaccination with the HA mixture could boost immune responses against the stalk without negatively affecting head-specific responses. This translated into superior protection against homologous and heterologous influenza challenges in mice and ferrets, supporting further development of this remixed influenza vaccine. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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