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Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses
- Source :
- Immunity. 55:2405-2418.e7
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominant yet conserved HA stem harbors a supersite that is targeted by broadly neutralizing antibodies (bnAbs), representing a prime target for universal vaccines. Here, we showed that the co-immunization of two HA stem immunogens derived from group 1 and 2 influenza A viruses elicits cross-group protective immunity and neutralizing antibody responses in mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected from multiple group 1 and 2 viruses, and all animal models showed broad serum-neutralizing activity. A bnAb isolated from an immunized NHP broadly neutralized and protected against diverse viruses, including H5N1 and H7N9. Genetic and structural analyses revealed strong homology between macaque and human bnAbs, illustrating common biophysical constraints for acquiring cross-group specificity. Vaccine elicitation of stem-directed cross-group-protective immunity represents a step toward the development of broadly protective influenza vaccines.
- Subjects :
- Influenza A Virus, H5N1 Subtype
Immunology
Ferrets
Hemagglutinin Glycoproteins, Influenza Virus
Influenza A Virus, H7N9 Subtype
Antibodies, Viral
Antibodies, Neutralizing
Mice
Hemagglutinins
Infectious Diseases
Orthomyxoviridae Infections
Influenza Vaccines
Influenza, Human
Animals
Humans
Immunology and Allergy
Immunization
Broadly Neutralizing Antibodies
Subjects
Details
- ISSN :
- 10747613
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....899d5e8d1648c011a3a8751d2c439bfc