A novel combination of intramuscular vaccine adjuvants, nanoemulsion and CpG produces an effective immune response against influenza A virus

Su He Wang; Jesse Chen; Douglas Smith; Zhengyi Cao; Hugo Acosta; Yongyi Fan; Susan Ciotti; Ali Fattom; James Baker Jr

doi:10.1016/j.vaccine.2020.03.026

A novel combination of intramuscular vaccine adjuvants, nanoemulsion and CpG produces an effective immune response against influenza A virus

Vaccine. 2020 Apr 23;38(19):3537-3544. doi: 10.1016/j.vaccine.2020.03.026. Epub 2020 Mar 31.

Authors

Su He Wang¹, Jesse Chen¹, Douglas Smith², Zhengyi Cao¹, Hugo Acosta², Yongyi Fan¹, Susan Ciotti², Ali Fattom², James Baker Jr¹

Affiliations

¹ Michigan Nanotechnology Institute for Medicine and Biological Sciences, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States.
² BlueWillow Biologic, Ann Arbor, MI, United States.

PMID: 32245642
DOI: 10.1016/j.vaccine.2020.03.026

Abstract

Background: Vaccination is the most effective approach to prevent infection with highly pathogenic avian influenza (HPAI). Adjuvants are often used to induce effective immune responses and overcome the immunological weakness of recombinant HPAI antigens. Given the logistical challenges of immunization to HPAI during pandemic situations, vaccines administered via the intramuscular (I.M.) route would be of value.

Methods: A new formulation of nanoemulsion adjuvant (NE02) suitable for I.M. vaccination was developed. This NE02 was evaluated alone and in combination with CpG to develop H5 immune responses in mouse and ferret models. Measures of recombinant H5 (rH5) specific immunity evaluated included serum IgG and IgG subclasses, bronchoalveolar lavage fluid IgA, and cytokines. The activation of NF-kB was also analyzed. The efficacy of the vaccine was assessed by performing hemagglutination inhibition (HAI), virus neutralization (VN) assays, and viral challenges in ferrets.

Results: I.M. vaccination with rH5-NE02 significantly increased rH5-specific IgG and protected ferrets in the viral challenge model providing complete protection and sterile immunity in all animals tested. Combining NE02 and CpG produced accelerated antibody responses and this was accompanied by an elevation of IFN-γ and IL-17 responses and the downregulation of IL-5. The combination also caused a synergistic effect on NF-kB activation. In immunized ferrets after viral challenge, the rH5-NE02 + CpG vaccine via I.M. achieved at least 75% and 88% seroconversion of HAI and VN antibody responses, respectively, and improved body temperature stabilization and weight loss over NE02 alone.

Conclusions: The I.M. injection of NE02 adjuvanted rH5 elicits strong and broad immune responses against H5 antigens and effectively protects animals from lethal H5 challenge. Combining this adjuvant with CpG enhanced immune responses and provided improvements in outcomes to viral challenge in ferrets. The results suggest that combinations of adjuvants may be useful to enhance H5 immune responses and improve protection against influenza infection.

Keywords: CpG; Ferret; Influenza A virus; Intramuscular adjuvant; Nanoemulsion.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Animals
Antibodies, Viral
Ferrets
Influenza A Virus, H5N1 Subtype*
Influenza A virus*
Influenza Vaccines*
Mice
Orthomyxoviridae Infections* / prevention & control

Substances

Adjuvants, Immunologic
Antibodies, Viral
Influenza Vaccines