Important note: Information in this article was accurate in January 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, January 18, 1999
Daniel J. DeNoon, Senior Editor
Prototype AIDS vaccines can protect cats against feline immunodeficiency virus (FIV). The animals have a robust antibody response to vaccination. But extensive analysis by an Italian research team has failed to identify even a single correlation between humoral immune responses and protection.
"Despite the wide spectrum of parameters investigated, no correlation between vaccine-induced protection and the humoral parameters was noted," sighed University of Pisa researchers Paola Mazzetti, Mauro Bendinelli, and colleagues.
Mazzetti reported their findings in the Journal of Virology ("AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Model: Detailed Analysis of the Humoral Immune Response to a Protective Vaccine," J Virol, 1999;73(1):1-10).
The study seemed ideally suited to tease out some of the long- sought correlates of immunity to HIV. The cat/FIV model has a long history in AIDS research. Recently, the Italian researchers reported that a fixed-cell FIV vaccine could protect specific-pathogen-free (SPF) cats against cell-free and cell-associated challenge with homologous, wild-type, fully virulent FIV (Matteucci, D. et al. J Virol, 1997;71:8368-76).
Although the cats were fully protected and completely cleared the challenge virus, protection was relatively brief.
"Vaccinees proved totally protected against cell-free virus when challenged 4 months after completion of the primary vaccination series but not when the same virus was given at 12 or 28 months, despite the fact that 2 months prior to challenge the animals had received a booster vaccine dose," Mazzetti et al. wrote. "In addition, vaccinees proved to be protected against cell-associated virus at 12 months after completion of primary vaccination but not at 3 years, in spite of a booster given 10 weeks before the latter challenge."
Frequent samples taken from the animals offered the hope that correlates of humoral protection could be found. Mazzetti et al. conducted an extensive series of tests.
Antibody binding assays included quantitative Western blotting, enzyme-linked tests for antibodies to FIV glycoproteins and immunodominant linear epitopes, and measures of conformation dependence and avidity of anti-Env antibodies.
Functional assays included virus neutralization studies (using two different cell substrates), complement- and antibody-dependent virolysis, reverse-transcriptase blocking, and the ability of sera to prevent FIV growth in cell culture.
None of these results correlated with protection. Mazzetti et al. noted that they did not test the sera for antibody-mediated, cell- dependent cytotoxic activity against target cells infected with FIV, and thus may have missed one potential mechanism. But they were left with the general impression that the role of humoral immunity in protection was far more complex than any single assay could measure.
"Finally, a possibility that appears most likely is that to achieve protection antibodies must work in concert with other immune and nonimmune effector functions in complex ways that currently available assays cannot reproduce," they wrote.
This work was supported by grants from the Ministero della Sanita- Istituto Superiore di Sanita Programma per l'AIDS and by the Ministero della Universita e Ricerca Tecnologica, Rome, Italy.
The corresponding author for this study is Mauro Bendinelli, Dipartimento di Biomedicina, Universita di Pisa, Via San Zeno 37, I- 56127 Pisa, Italy. Phone: 39-050-553562. Fax: 39-050-556455. Email: <bendinelli@biomed.unipi.it>.
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