Egan Michael A, Chong Siew Yen, Hagen Michael, Megati Shakuntala, Schadeck Eva B, Piacente Priscilla, Ma Ben-Jiang, Montefiori David C, Haynes Barton F, Israel Zimra R, Eldridge John H, Staats Herman F
Wyeth Vaccines Research, Pearl River, NY 10965, USA.
Vaccine. 2004 Sep 9;22(27-28):3774-88. doi: 10.1016/j.vaccine.2004.03.011.
Cynomolgus macaques were immunized by either the intramuscular (i.m.) or intranasal (i.n.) route with a HIV-1 peptide-based immunogen (C4-V3 89.6P) alone, or formulated with novel adjuvants to evaluate the ability of the adjuvants to augment peptide-specific systemic and mucosal immune responses. A mutant cholera toxin, CT-E29H, or the combination of recombinant human IL-1alpha (rhIL-1alpha) protein and recombinant human GM-CSF (rhGM-CSF) protein were tested as adjuvants for i.n. immunization, while a stable emulsion of a synthetic monophosphoryl lipid A (MPL) analogue (RC529-SE) plus rhGM-CSF protein was tested as an adjuvant for i.m. immunization. Macaques immunized i.n. with peptide alone failed to elicit an anti-C4-V3 89.6P antibody response in serum. In contrast, all the tested peptide/adjuvant formulations elicited peptide-specific immune responses. RC529-SE/rhGM-CSF elicited the highest peak anti-peptide IgG geometric mean titer in serum (1:32,768 at week 25) followed by rhIL-1alpha/rhGM-CSF (1:1217 at week 10) and CT-E29H (1:256 at week 25). Measurable SHIV neutralizing antibody responses were detectable in only one macaque immunized i.m. with peptide formulated with RC529-SE/rhGM-CSF. Macaques immunized by the i.n. route with peptide in combination with CT-E29H failed to elicit measurable antibody responses at nasal or genital mucosal surfaces. In contrast, antibody responses at the nasal and genital mucosa were detected in macaques immunized by the i.n. route with peptide in combination with rhIL-1alpha/rhGM-CSF. However, antibody responses at the nasal and genital mucosa were highest in macaques immunized parenterally with peptide in combination with the adjuvants RC529-SE/rhGM-CSF. These results suggest that parenteral vaccine administration in combination with the appropriate adjuvant formulation can elicit vaccine-specific humoral immune responses in both systemic and mucosal compartments.
食蟹猴通过肌肉注射（i.m.）或鼻内（i.n.）途径，单独使用基于HIV-1肽的免疫原（C4-V3 89.6P）进行免疫，或与新型佐剂一起配制，以评估佐剂增强肽特异性全身和黏膜免疫反应的能力。测试了一种突变霍乱毒素CT-E29H，或重组人IL-1α（rhIL-1α）蛋白与重组人GM-CSF（rhGM-CSF）蛋白的组合作为鼻内免疫的佐剂，而合成单磷酰脂质A（MPL）类似物（RC529-SE）加rhGM-CSF蛋白的稳定乳剂则作为肌肉注射免疫的佐剂进行测试。单独用肽进行鼻内免疫的食蟹猴未能在血清中引发抗C4-V3 89.6P抗体反应。相比之下，所有测试的肽/佐剂配方均引发了肽特异性免疫反应。RC529-SE/rhGM-CSF在血清中引发的抗肽IgG几何平均滴度峰值最高（第25周时为1:32,768），其次是rhIL-1α/rhGM-CSF（第10周时为1:1217）和CT-E29H（第25周时为1:256）。仅在一只通过肌肉注射用RC529-SE/rhGM-CSF配制的肽进行免疫的食蟹猴中检测到了可测量的SHIV中和抗体反应。用肽与CT-E29H组合通过鼻内途径免疫的食蟹猴在鼻或生殖器黏膜表面未能引发可测量的抗体反应。相比之下，在用肽与rhIL-1α/rhGM-CSF组合通过鼻内途径免疫的食蟹猴中检测到了鼻和生殖器黏膜的抗体反应。然而，在用肽与佐剂RC529-SE/rhGM-CSF组合进行肠胃外免疫的食蟹猴中，鼻和生殖器黏膜的抗体反应最高。这些结果表明，肠胃外疫苗接种与适当的佐剂配方相结合，可以在全身和黏膜区室中引发疫苗特异性体液免疫反应。
