Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX™ adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques.
There is a need for novel rabies vaccines suitable for short course, pre- and post-exposure prophylactic regimens which require reduced doses of antigen to address the current worldwide supply issue. We evaluated in rhesus macaques the immunogenicity of a quarter-dose of a standard rabies vaccine formulated with Merck's amorphous aluminum hydroxylphosphate sulfate adjuvant, the saponin-based ISCOMATRIX™ adjuvant, or a synthetic TLR9 agonist. All adjuvants significantly increased the magnitude and durability of the humoral immune response as measured by rapid fluorescent focus inhibition test (RFFIT). Several three-dose vaccine regimens resulted in adequate neutralizing antibody of ≥ 0.5 IU/ml earlier than the critical day seven post the first dose. Rabies vaccine with ISCOMATRIX™ adjuvant given at days 0 and 3 resulted in neutralizing antibody titers which developed faster and were up to one log10 higher compared to WHO-recommended intramuscular and intradermal regimens and furthermore, passive administration of human rabies immunoglobulin did not interfere with immunogenicity of this reduced dose, short course vaccine regimen. Adjuvantation of whole-killed rabies vaccine for intramuscular injection may therefore be a viable alternative to intradermal application of non-adjuvanted vaccine for both pre- and post-exposure regimens.
Department of Vaccine Basic Research, Merck Research Laboratories, West Point, PA, USA.
Daniel
D
DiStefano
Joseph M
JM
Antonello
Andrew J
AJ
Bett
Muneeswara B
MB
Medi
Danilo R
DR
Casimiro
Jan
J
ter Meulen
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D017607:Aluminum Compounds / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002784:Cholesterol / Q000008:administration & dosage*; D004338:Drug Combinations; D005260:Female; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D010710:Phosphates / Q000008:administration & dosage; D010743:Phospholipids / Q000008:administration & dosage*; D011818:Rabies / Q000517:prevention & control; D011819:Rabies Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D012503:Saponins / Q000008:administration & dosage*; D013431:Sulfates / Q000008:administration & dosage; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; C493786:ISCOMATRIX; D010710:Phosphates; D010743:Phospholipids; D011819:Rabies Vaccines; D012503:Saponins; D013431:Sulfates; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D015164:Vaccines, Inactivated; D002784:Cholesterol