Subunit vaccines containing one or more target antigens from pathogenic organisms
represent safer alternatives to whole pathogen vaccines. However, the antigens by
themselves are not sufficiently immunogenic and require additives known as adjuvants
to enhance immunogenicity and protective efficacy. Assembly of the antigens into virus-like
nanoparticles (VLPs) is a better approach as it allows presentation of the epitopes
in a more native context. The repetitive, symmetrical, and high density display of
antigens on the VLPs mimic pathogen-associated molecular patterns seen on bacteria
and viruses. The antigens, thus, might be better presented to stimulate host's innate
as well as adaptive immune systems thereby eliciting both humoral and cellular immune
responses. Bacteriophages such as phage T4 provide excellent platforms to generate
the nanoparticle vaccines. The T4 capsid containing two non-essential outer proteins
Soc and Hoc allow high density array of antigen epitopes in the form of peptides,
domains, full-length proteins, or even multi-subunit complexes. Co-delivery of DNAs,
targeting molecules, and/or molecular adjuvants provides additional advantages. Recent
studies demonstrate that the phage T4 VLPs are highly immunogenic, do not need an
adjuvant, and provide complete protection against bacterial and viral pathogens. Thus,
phage T4 could potentially be developed as a "universal" VLP platform to design future
multivalent vaccines against complex and emerging pathogens.