Minimal immunogen
vaccines are being developed to focus antibody
responses against otherwise challenging targets, including human immunodeficiency
virus (HIV), but multimerization of the minimal peptide immunogen
on a carrier platform is required for activity. Star copolymers comprising
multiple hydrophilic polymer chains (“arms”) radiating
from a central dendrimer unit (“core”) were recently
reported to be an effective platform for arraying minimal immunogens
for inducing antibody responses in mice and primates. However, the
impact of different parameters of the star copolymer (e.g., minimal
immunogen density and hydrodynamic size) on antibody responses and
the optimal synthetic route for controlling those parameters remains
to be fully explored. We synthesized a library of star copolymers
composed of poly[N-(2-hydroxypropyl)methacrylamide]
hydrophilic arms extending from poly(amidoamine) dendrimer cores with
the aim of identifying the optimal composition for use as minimal
immunogen vaccines. Our results show that the length of the polymer
arms has a crucial impact on the star copolymer hydrodynamic size
and is precisely tunable over a range of 20–50 nm diameter,
while the dendrimer generation affects the maximum number of arms
(and therefore minimal immunogens) that can be attached to the surface
of the dendrimer. In addition, high-resolution images of selected
star copolymer taken by a custom-modified environmental scanning electron
microscope enabled the acquisition of high-resolution images, providing
new insights into the star copolymer structure. Finally, in
vivo studies assessing a star copolymer vaccine comprising
an HIV minimal immunogen showed the criticality of polymer arm length
in promoting antibody responses and highlighting the importance of
composition tunability to yield the desired biological effect.