IAVI Report Vo. 5, no. 2

PARIS VACCINE MEETING
continued from page 5

given a recombinant envelope gp90 subunit vaccine and then
challenged with homologous virus (the one used to make
vaccine) showed signs of more severe disease, while 5 had
the typical disease course and 3 showed some protection.
One animal died within two weeks after a challenge with
heterologous virus (of a different strain), something that rarely
happens, with a viral load 100-1000 times higher
than that in unvaccinated animals. Yet antiserum from that
horse caused less than a 2-fold increase in viral replication
in vitro, showing that this assay does not reflect diseaseenhancing potential.
Other studies on the EIAV system have used these different
types of vaccines to look for correlates of protection.
Montelaro said that no single parameter emerged as a reliable
correlate, although there was a general trend towards better
protection with more mature antibodies (those with higher
avidity and conformational dependence, which appear later
in a humoral response). That led to his conclusion: HIV
vaccine designs should aim at accelerating antibody
maturation, using approaches such as sustained antigen
presentation or prime-boost regimens that seem to drive
maturation forward more rapidly.
Pierre Sonigo (Institut Cochin de Gen&ique Mol&culaire,
Paris) also spoke about enhancement of infection in animals, in
this case with DNA vaccines against feline immunodeficiency
virus (FIV). But these vaccines do not induce antibodies,

which means that there must be other factors that can lead to
enhancement. Further studies (not in the FIV system) showed
that one such factor is IL-12, a cytokine made after immune
stimulation. That result suggests a paradox: immune activation
(with release of cytokines) is necessary to generate protective
responses, but may also contribute to enhancement. Sonigo
concluded that antibody function reflects a balance between
enhancement and protection.
The session ended with some concern in the air over
whether HIV vaccines could lead to disease enhancement, but
no additional in vivo data emerged from the question-andanswer period. (For further discussion, see "Enhancing
Antibodies - A Concern for HIV Vaccine Trials?," page 5. For
comprehensive reviews on enhancement, see Mascola et al.,
AIDS Research and Human Retroviruses 9, 1175, 1993; Burke,
Perspectives in Biology and Medicine 35: 511, 1992.)
Making better antigens
The remaining talks on antibodies presented various strategies
for making better antigens, work mostly in very early stages.
Indresh Srivastava of Chiron (Emeryville, California) described
the company's studies comparing oligomeric envelope (gp140)
with monomeric gp120. Both proteins can be mass-produced
and purified in what look like authentic versions (based on
glycosylation patterns, CD4- and antibody-binding patterns); in
rabbits, the gp140 elicits high-avidity neutralizing antibodies

continued on page 13

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