(AW) Conference Coverage (NCVDG): Goat Virus May Protect Against HIV

AIDSWEEKLY Plus, Monday, 2 June 1997

Daniel J. DeNoon, Senior Editor

--------------------------------------------------------------------------------

Humans infected with a harmless goat virus develop antibodies that neutralize HIV.

The remarkable finding offers hope for a safe, attenuated AIDS vaccine using the goat virus or a
genetically engineered variant carrying HIV genes. It is strikingly reminiscent of the earliest
vaccine: Edward Jenner's discovery that a relatively harmless cow virus (cowpox or vaccinia)
could protect humans against smallpox.

The goat virus is caprine arthritis-encephalitis virus (CAEV).

"A major obstacle to designing live attenuated vaccines using primate lentiviruses is the
substantial health threat to humans," noted Angeline Douvas of the University of Southern
California, Los Angeles.

"Human-infecting CAEV-like lentiviruses with low pathogenicity may have prophylactic

applications against HIV-1 as vaccines, as chimeras with HIV-1 (CHIVs), or as competitors for
binding to target-cell receptors."

Douvas reported the findings in a report to the 9th Annual Meeting of the National Cooperative
Vaccine Development Groups for AIDS (NCVDG), held May 4-7, 1997, in Bethesda, Maryland.

CAEV is a monocyte/macrophage-tropic virus with worldwide distribution. At least 65 percent

of goats carry the virus; some 85 percent of goat herds are infected. About 40 percent of infected
animals develop symptoms of arthritis, mastitis (breast inflammation), and/or encephalitis.

Human infection, which is non-pathogenic, occurs mainly through ingestion of raw goat milk.

CAEV variants capable of infecting humans were first detected in people with mixed connective
tissue disease (MCTD), an immune deficiency with clinical features similar to those of systemic
lupus erythematosus (SLE). But CAEV is not etiologically linked to MCTD, and human-
infecting variants (h- CAEV) have been isolated from healthy people, predominantly of Mexican
descent.

h-CAEV is endemic in Mexico; 24 to 39 percent of children with Mexican parents are

seropositive for CAEV.

DNA analysis shows that h-CAEV is similar to goat CAEV and is not a distinct lentivirus. h-
CAEV can be passed in culture to human peripheral blood mononuclear cells (PBMC) via
plasma from infected individuals.
Douvas and colleagues became interested in the potential of CAEV as an AIDS vaccine when
they learned that some Hispanic MCTD patients tested positive for anti-HIV antibodies even
though they were not infected with the AIDS virus.

They found that h-CAEV antibodies from some subjects reacted to both the CAEV gp135
surface glycoprotein and the HIV-1 gp120 envelope glycoprotein. Moreover, these anti-CAEV
antibodies were capable of "substantially neutralizing HIV-1."

Douvas's group analyzed antibody reactivity from four groups of human subjects:

* Hispanic MCTD patients (n=33). Antibodies from 91 percent recognized CAEV gp135, 61
percent recognized HIV gp120, and 65 percent had dual reactivity.

* Normal Hispanic volunteers (n=16). Antibodies from 63 percent recognized CAEV gp135, 25
percent recognized HIV gp120, and 40 percent had dual reactivity.

* People with occupational exposure to CAEV (n=2). Antibodies from both subjects recognized
CAEV gp135; one had antibodies that recognized HIV gp120 and one had antibodies with dual
reactivity.

* HIV-1 positive individuals (n=10). Antibodies from 10 percent recognized CAEV gp135, 100
percent recognized HIV gp120, and 10 percent had dual reactivity.

Douvas and colleagues hypothesized that h-CAEV variants that elicit both gp135 and gp120
antibodies (++ variants) arose from a combination of variants that recognized only CAEV gp135
(+- variants) or only HIV gp120 (-+ variants). They further suggested that the ++ variants have
structures resembling gp120.

Analysis of CAEV strains from goats and sheep shows that they carry motifs that have been
associated with macrophage- tropic strains of HIV-1. These strains currently are thought to be
responsible for the vast majority of HIV infections.

Douvas suggested that CAEV variants potentially could be used as a live attenuated vaccine for
AIDS. The immunity elicited by such vaccines could be increased by creating chimeric
CAEV/HIV variants (CHIV). In addition to eliciting antibody responses that could protect
against HIV, CAEV might block the cellular receptors HIV needs to establish infection.

Of great interest to vaccine studies is the finding that macaque monkeys can be infected with h-
CAEV, paving the way for studies in a relevant animal model.

970602
AW970601

http://www.aegis.com/default.asp?req=http://www.aegis.com/pubs/aidswkly/1997/AW970601.ht
ml