The search for
vaccines that protect from severe
morbidity and
mortality as a result of
infection with
severe acute respiratory syndrome coronavirus 2 (
SARS-CoV-2 ), the
virus that causes coronavirus disease 2019 (COVID-19) is a
race against the clock and the
virus . Several
vaccine candidates are currently being tested in the clinic. Inactivated
virus and
recombinant protein vaccines can be safe options but may require adjuvants to induce robust
immune responses efficiently. In this
work we describe the use of a novel amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a
cholesterol -poly(
ethylene glycol ) macromolecular amphiphile). This amphiphile is
water soluble and exhibits massive translocation to
lymph nodes upon local
administration , likely through binding to
albumin . IMDQ-PEG-CHOL is used to induce a protective
immune response against
SARS-CoV-2 after single
vaccination with trimeric recombinant
SARS-CoV-2 spike
protein in the BALB/c
mouse model. Inclusion of amphiphilic IMDQ-PEG-CHOL in the
SARS-CoV-2 spike
vaccine formulation resulted in enhanced immune
cell recruitment and activation in the draining
lymph node . IMDQ-PEG-CHOL has a better
safety profile compared to native soluble IMDQ as the former induces a more localized
immune response upon local
injection , preventing systemic
inflammation . Moreover, IMDQ-PEG-CHOL adjuvanted
vaccine induced enhanced
ELISA and
in vitro microneutralization titers, and a more balanced
IgG2a /
IgG1 response. To correlate
vaccine responses with
control of
virus replication in vivo, vaccinated
mice were challenged with
SARS-CoV-2 virus after being sensitized by intranasal
adenovirus -mediated expression of the
human angiotensin converting enzyme 2 (ACE2)
gene .
Animals vaccinated with trimeric recombinant spike
protein vaccine without adjuvant had
lung virus titers comparable to non-vaccinated
control mice , whereas
animals vaccinated with IMDQ-PEG-CHOL-adjuvanted
vaccine controlled
viral replication and infectious
viruses could not be recovered from their
lungs at day 4 post
infection . In order to test whether IMDQ-PEG-CHOL could also be used to adjuvant
vaccines currently licensed for use in
humans , proof of concept was also provided by using the same IMDQ-PEG-CHOL to adjuvant
human quadrivalent inactivated
influenza virus split
vaccine , which resulted in enhanced
hemagglutination inhibition titers and a more balanced
IgG2a /
IgG1 antibody response . Enhanced
influenza vaccine responses correlated with better
virus control when
mice were given a lethal
influenza virus challenge. Our results underscore the potential use of IMDQ-PEG-CHOL as an adjuvant to achieve
protection after single
immunization with
recombinant protein and
inactivated vaccines against respiratory
viruses , such as
SARS-CoV-2 and
influenza viruses .