TABLE 1.

Active Immunization using tau antigens

Authors	Antigen, Dose & Adjuvant	Mouse Model, incl. mutation, if present	Age at first inj	Duration	Techniques and markers examined	Details/Results
Asuni et al, J Neurosci 2007	100 μl Tau379–408 @ 1 mg/ml with Adju-Phos adjuvant, sc bi-weekly for first month, then monthly	JNPL3 (P301L)	2 mo	3 – 5 mo	IHC and Western Blot for MC-1 & PHF1, Rotarod, NOR	↓ MC-1 and PHF 1 by IHC; ↑ PHF 1 in soluble fraction by Western, ↑ time on rotarod; No cognitive change in NOR; noted antibody uptake into neurons
Boutajangout, et al, J Neurosci 2010	100 μg Tau379–408 + 100 μl Alum, i.p.; 3 injections bi-weekly, then monthly	hTau/PS1	3–4 mo	5 – 6 mo	IHC for PHF1 & AT8, PHF1 by Western, Rotarod, Traverse Beam RAM, NOR, CFSM	↓ PHF1 and AT8, ↓ soluble PHF1, no change in rotarod performance, improved performance in RAM and NOR
Boimel et al, Exp Neurol 2010	sc injection of 100 μg each of 3 KLH-linked phos-tau-peptides (aa’s ~ 195 – 238) with i.p. CFA + PT. Adjuvant booster @ 48 hrs, then sc antigen booster 1 wk later	E257T/P301S	4 to 12 mo	2 wks	Clinical evaluation of paralysis; Gallyas staining (NFT); IHC for AT8, AT180, and glial markers GFAP, MAC3, CD45R and CD4; Bielschowsky-Hematoxylin and lectin staining; double immunofluorescence for CD11b, F4/80 and MAC3; & lysosomal staining for Cathepsin D	No ↑ in paralysis; no difference in monocyte infiltration (Bielschowsky Hemotoxylin staining), CD45R & CD4 staining showed limited B or T cell infiltration, no macrophages detected by MAC3 & no axonal damage noted by these stains, so encephalogic risk is minimal; injected tau present in sera & blood, not parenchyma; ↓ NFTs, ↓ AT8, ↓ AT180, ↑ microglia by lectin staining, ↓ Cathepsin D
Bi et al, PLOS1 2011	100 μg KLH-linked peptide (aa’s 395–406) with CFA (first) then with IFA 2 & 4 wks after	pR5 (P301L)	4, 8, or 18 mo	1 mo	Gallyas staining for tangles, IHC for PHF1 & pSer422, GFAP staining	↓ NFTs, PHF1 and pSer422; ↑ GFAP in old mice, trend ↑ in mid-aged mice, no difference in GFAP in young after vaccine
Troquier et al, Curr Alz Res 2012	100 μg Y14T or Y10A (pSer422 epitope) i.p. + CFA; 2nd injection 2 wks later with IFA, then monthly	THY-Tau22 (4R @ g272v & p301S with Thy 1.2 promoter)	2 or 3.5 mos	14 wks or 18 wks	IHC, Modified Y-maze, ELISA, Western	No changes in AT8, ↓ in AT100 & pSer422, vaccines ↑ performance to wt levels, ↑ tau in sera in correlation with duration of treatment & memory performance, ↓ AT100 & pSer422 in SDS-insoluble fraction
Rozenstein-Tsalkovich et al, Exp Neurol 2013	Sc injection of 3 phos-tau-peptides @ 100 μg, in IFA and PT, given twice bi-weekly, then 50 μl peptide monthly	E257T/P301S	6 or 12 mos	8 – 14 wks	Experimental autoimmune encephalomyelitis test, IHC, behavioral observation	↑ monocyte infiltration with memory improvement, no microglial change, treated mice developed paralysis
Selenica et al, J Neuroinflam 2014	Sc administration of 100 μg tau (human wt or P301L tau) with 20 μg Quil-A adjuvant. 3 bi-weekly injections followed with a 10 -week resting period then boosters every 3 weeks for 3 additional times	rTg4510	5 mos	19 wks, including a 10-day resting period	[3-thymidine] assay to identify T-cell proliferation; epitope mapping via microarray; IHC for tau species, and glial markers CD45, CD11b and GFAP	↑ antibody production, ↑ cellular response: ↓ CD45, CD11b and GFAP; ↓ H150 & AT8; 5 new immunogenic epitopes identified by microarray: 2 N-terminal (aa’s 9–15 and 21–27), two in the proline-rich domain (aa’s 168–174 and 220–228) and 1 in the C-terminal (aa’s 427–438); 5 new immunogenic epitopes were identified: 2 N-terminal (aa’s9–15 and 21–27), two in the proline-rich domain (aa’s 168–174 and 220–228) and 1 in the C-terminal (aa’s 427–438)

Notes:

sc = subcutaneous

i.p. = intraperitoneal

IHC = immunohistochemistry

NOR = Novel Object Recognition

RAM = Radial Arm Maze

CFSM = Closed Field Symmetrical Maze

KLH = keyhole limpet hemocyanin

aa’s = amino acids

CFT = complete Freund’s adjuvant

PT = pertussis toxin

IFA = incomplete Freund’s adjuvant

NFT = neurofibrillary tangles

GFAP = glial fibrillary acidic protein

wt = wild-type