15 March 2004. A multi-institutional collaboration led by Sam Gandy at Thomas Jefferson University, Philadelphia, has vaccinated rhesus monkeys (Macaca mulatta) against the Aβ peptide in an effort to establish a more human-like animal model than mice for use in vaccination studies. Their first results, demonstrating that rhesus monkeys can mount an antibody response to Aβ, appear the January-March issue of Alzheimer Disease and Associated Disorders.
Gandy immunized four monkeys, two with aggregated Aβ1-42, and two with aggregated islet amyloid polypeptide (amylin). Six months later, the researchers measured plasma Aβ levels in the animals and found dramatic increases in plasma Aβ in the two monkeys vaccinated with the Aβ aggregate. These animals had about fivefold more Aβ circulating in their plasma and much of it (49 and 36 percent for each) was bound to IgG. Looking at the brain levels of Aβ and cytokines, the authors found similar amounts in all four animals. The failure to detect a decline in brain Aβ is not necessarily bad news, the scientists write, as these animals were not old enough to have detectable Aβ deposits. Their hippocampi showed no amyloid, glial, or immune pathology.
The authors offer this primate model as an aid to designing human vaccines. The animals showed no sign of encephalitis, and it is uncertain as yet if rhesus monkeys can recapitulate this side effect seen in humans (17 cases of encephalitis prompted termination of dosing in a phase IIa trial of Elan's 1792 vaccine; (see ARF related news story). In one respect, these animals did react differently from humans, as the elevation in serum Aβ was not seen in human trial volunteers (see Hock et al., 2002 and ARF related news story); this may indicate that monkeys and humans respond differently to vaccination.—Tom Fagan.
Gandy S, DeMattos RB, Lemere CA, Heppner FL, Leverone J, Aguzzi A, Ershler WB, Dai J, Fraser P, St. George-Hyslop P, Holtzman DM, Walker LC, Keller ET. Alzheimer Aβ Vaccination of Rhesus Monkeys (Macaca mulatta). Alzheimer Dis. Assoc. Disord. 2004 January-March. 303:44-46. Abstract