Induction of Cross-Reactive Hemagglutination Inhibiting Antibody and Polyfunctional CD4+ T-Cell Responses by a Recombinant Matrix-M-Adjuvanted Hemagglutinin Nanoparticle Influenza Vaccine.

Abstract

BACKGROUND:

Recurrent reports of suboptimal influenza vaccine effectiveness have renewed calls to develop improved, broadly cross-protective influenza vaccines. Here, we evaluated the safety and immunogenicity of a novel, saponin (Matrix-M)-adjuvanted, recombinant hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV).

METHODS:

We conducted a randomized, observer-blind, comparator-controlled (trivalent high-dose inactivated influenza vaccine [IIV3-HD] or quadrivalent recombinant influenza vaccine [RIV4]), safety and immunogenicity trial of qNIV (5 doses/formulations) in healthy adults ≥65 years. Vaccine immunogenicity was measured by hemagglutination-inhibition assays using reagents that express wild-type hemagglutination inhibition (wt-HAI) sequences and cell-mediated immune responses.

RESULTS:

A total of 1375 participants were randomized, immunized, and followed for safety and immunogenicity. Matrix-M-adjuvanted qNIV induced superior wt-HAI antibody responses against 5 of 6 homologous or drifted strains compared with unadjuvanted qNIV. Adjuvanted qNIV induced post-vaccination wt-HAI antibody responses at day 28 that were statistically higher than IIV3-HD against a panel of homologous or drifted A/H3N2 strains, similar to IIV3-HD against homologous A/H1N1 and B (Victoria) strains and similar to RIV4 against all homologous and drifted strains evaluated. The qNIV formulation with 75 µg Matrix-M adjuvant induced substantially higher post-vaccination geometric mean fold increases of influenza HA-specific polyfunctional CD4+ T cells compared with IIV3-HD or RIV4. Overall, similar frequencies of solicited and unsolicited adverse events were reported in all treatment groups.

CONCLUSIONS:

qNIV with 75 µg Matrix-M adjuvant was well tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses. Further investigation in a pivotal phase 3 trial is underway.

CLINICAL TRIALS REGISTRATION:

NCT03658629.

• Authors: Vivek Shinde, Rongman Cai, Joyce Plested, Iksung Cho, Jamie Fiske, Xuan Pham, Mingzhu Zhu, Shane Cloney-Clark, Nan Wang, Haixia Zhou, Bin Zhou, Nita Patel, Michael J Massare, Amy Fix, Michelle Spindler, David Nigel Thomas, Gale Smith, Louis Fries, Gregory M Glenn
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 73 Issue 11 Pg. e4278-e4287 (12 06 2021) ISSN: 1537-6591 [Electronic] United States
• PMID: 33146720 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Antibodies, Viral
• Hemagglutinins
• Influenza Vaccines
• Matrix-M
• Saponins
• Vaccines, Inactivated

Topics

• Adult
• Antibodies, Viral
• CD4-Positive T-Lymphocytes
• Hemagglutination
• Hemagglutination Inhibition Tests
• Hemagglutinins
• Humans
• Immunogenicity, Vaccine
• Influenza A Virus, H1N1 Subtype
• Influenza A Virus, H3N2 Subtype
• Influenza Vaccines
• Influenza, Human (prevention & control)
• Nanoparticles
• Saponins
• Vaccines, Inactivated