IAVI Report Vol. 2, no. 2

AIDS Vaccine Conference Report continued from page 3
A number of adjuvants and cytokines are being studied for their ability
to increase the immunogenicity of DNA vaccines. Researchers at the
University of Massachusetts Medical Center and Aquila Biopharmaceuticals
of Worcester, Massachusetts (USA) reported that injecting mice
subcutaneously with the adjuvant QS-21 and a DNA vaccine (encoding for
gp 120) could generate nine-fold higher levels of antibodies than the DNA
vaccine alone.
Another poster presentation examined the use of various cytokines to
modify the immunogenicity of DNA vaccines. Researchers from the Karolinska
Institute and the Yokohama University School of Medicine evaluated a DNA
vaccine (containing the HIV genes env and rev) with a number of different
expression plasmids encoding cytokines. Of the cytokines used, interleukin- 12
(IL-12) and IL-2 increased CTL response, while IL-4 and alpha interferon
improved antibody responses.
A unique approach to DNA immunization is to create libraries of fragments
of HIV genes and to express them in DNA vaccines. Stephen Johnston of the
Southwestern Medical Center gave an update on this approach. Johnston
reported that by fragmenting the gag gene, new CTL epitopes were identified,
which, it is hoped, will elicit stronger CTL responses. To explore this strategy
further, libraries of fragments from HIV- I and HIV-2 were then created and
inoculated into baboons. One group of these baboons also received cytokine
adjuvants (GMCSF and IL-12). Antibodies to gag, pol and nef and CTLs to gag
were observed. If Johnston's approach can successfully protect primates, it is
likely to attract far greater attention.
A poster from Christopher Locher of the University of California at San
Francisco (working with Stephen Johnston) reported that an HIV-2 DNA
vaccine based on HIV-2 expression libraries induced an antibody response
to gag and pol after only one immunization.
Genetically attenuated, or "mutant", SIV DNA may hold promise as a
vaccine, according to a report by Larry Arthur, of the National Cancer
Institute. The SIV vaccine contains a mutation that results in production

of non-infectious particles. Arthur inoculated five macaques with mutant SIV
DNA. None of the monkeys showed signs of productive SIV infection. As a
control, four animals were vaccinated with plasmid DNA containing no SIV
genes. Upon challenge, the four control animals all had high levels of SIV,
whereas four of the five vaccinated monkeys had reduced or undetectable
levels of virus.
Lipid-based delivery formulations of DNA vaccines can induce strong
antibody and CTL responses in mice, according to a report by Susan Gould
Fogerite of UMDNJ-New Jersey Medical School. Fogerite reported that
lipid-based carriers, known as "cochleates", can deliver significantly higher
levels of DNA plasmid in the body, thus requiring less actual DNA to be
used. In addition, cochleate-based vaccines can be administered orally. The
cochleate technology is licensed to Wyeth-Lederle Vaccines and a small
study of the technology has been recently initiated in monkeys.
Live-Attenuated Vaccines
Studies continue to show that live-attenuated SIV vaccines can protect
against pathogenic SIV by preventing disease progression. There was much
discussion about conducting additional safety studies of these vaccines in
animals (see IAVI Report, vol. 2, no. 1). Such tests could include multiple
transfer experiments to evaluate whether the vaccines could revert to
pathogenic virus and explore whether particular subpopulations may be
unable to control the attenuated vaccine virus. In addition to safety studies,
efforts to determine the correlates of protection from live-attenuated SIV
vaccines are being conducted by researchers in many parts of the world.
In an effort to develop live-attenuated vaccines with even better safety
profiles, researchers at the University of California at Davis, led by Tilhuan
Yilma, deleted the SIV nef gene and replaced it with a gene expressing
gamma interferon. Yilma reported that, in comparison to the nef-deleted
and triple-gene deleted SIV vaccines, the new construct generated lower
levels of SIV in monkeys. In addition, he suggested that, unlike other liveattenuated vaccines, high doses of the gamma interferon vaccine appear

H IVC a e 4 a B ir lv ntt a cneD sg yPeggy ohnston, p.
Anmer 4;f repot peented- at the NCVDG meeting, anfets sugetthat vcieswould have'to be made fo h I
lewb e,suggest tat mght" be -possibl t esign,an 11W vyaccine chid e circulatinginteartpouton
that haswd s gis ay(nprasal 1- eei ldes' oweverthere are aeantibodies'from infected individuals t~,(or0 b~s) ~ eutaieprimary isolates of different HIV clades., In additionstde
Whith crrlaesofimmune, protec'tion'-against 11W remain,,>,of newervaccinqe designs, sch as compeed or oli'g'omeric fRmof
unkno',; % t muoloi mauemnsin )recipients of envelopesget that at naiemethods of presenting the e;ilyp t
exerinntilvacin s have focused nnurlzn niois(b evloet h muesse ih edto'ore bradly reatv
a n d - y m ~ o y e ( CT )f u t r a l i z n g b a r et h o g t t oa t b o i s U t l s u h ' e t o s a r o k e u, t w l l r m i
be i~orant r~ lockng nfetionof ells1y ~reevirs prtices. impotan tobase antibodoy-inducing vaccines on loa6 sbyps;,' CTLs'a'bled 6o6,be' porftant i eiintig1W-nfected cels 2' Until iecently data on the'ability of 11W-specific CT1.s'from on
r '4iss
SineiIVexitsinbot 'el-fre ndcel-as6ciated for ' n1ifete 'ddeto il clls infected -with a differentcdade of 11W has notbee
indiiul aybleeta ohbadCLrsosswl e 'vial.4However,'at the NCVDG meeting, Huyen"Cao of
neesr 'oachievepotcio-alhuh hrei:cerl oMassachuset General, Hospital'presented data demonstrating ta
co sns..on ti oit Tsfrom intdividuals, infected with cdade B HIV.killed cells'infce
'To6.aenidate11Wtvaccines, have, been bet eeae 'iha numtber''of, different HIlV clades, including A, and G fro
antboiescaabe o~nutaliin oly laboraorystrains of 1W ',,' Afti in additionh, CTLs from individuals infected, with'nn-ad'
baked on,the'same daide a te'acie hoolgosvirs).These '; HIV frequeintly killed cells'infected with dlade B'virus. iia eut
4 " 'th- ch*Oo6q squ-"iia