Gf. Arnold et al., CHIMERIC RHINOVIRUSES AS TOOLS FOR VACCINE DEVELOPMENT AND CHARACTERIZATION OF PROTEIN EPITOPES, Intervirology, 39(1-2), 1996, pp. 72-78
Chimeric human rhinoviruses (HRVs) have the potential to serve as vacc
ines against a wide variety of diseases. Such vaccines can be develope
d optimally by generating libraries of chimeric HRVs displaying immuno
gens from dangerous pathogens or tumor cells in many different conform
ations. Extremely large numbers of conformationally defined presentati
ons of foreign epitopes can be produced efficiently by flanking transp
lanted epitopes with linkers, or adapters, of small segments of random
ized amino acids. In addition, the individual residues of the immunoge
nic sequences can be encoded in proportion to their prevalence in data
bases. generating composite immunogens that function as mimotopes. The
diversity of sequences and conformations improves the likelihood of g
enerating immunologically valuable vaccine candidates. Chimeric viruse
s thus generated can be propagated and purified to select for viruses
whose growth and physical stability are like those of wild-type HRV. V
iruses containing a foreign epitope in antigenically relevant conforma
tions can then be captured by immunoselection with neutralizing antibo
dies directed against the foreign pathogen. Using this approach. we ha
ve been able to generate HRV chimeras that present V3 loop sequences o
f the human immunodeficiency virus type 1 (HIV-1) in immunologically r
elevant conformations. Antisera directed against such chimeras can neu
tralize multiple strains of HIV-1 in cell culture, suggesting that the
HRV 14:HIV-1 chimeras may be presenting their V3 loop sequences in ma
nners that mimic those of multiple strains of HIV. Immunologically int
eresting chimeras can be examined using X-ray crystallography to yield
detailed information about the structures of chimeras with immunogeni
c epitopes. This information may lead to a greater understanding of ke
y functional and structural elements of immunogenicity. The chimeric H
RV system allows one to present virtually any protein epitope or mimit
ope thereof, identify viruses with immunological characteristics that
mimic those of the foreign pathogen, and examine the structures of the
se immunogenic sequences at the atomic level.