Herrera Carolina, Veazey Ronald, Lemke Melissa M, Arnold Kelly, Kim Jerome H, Shattock Robin J
Department of Medicine, Imperial College London, London W2 1PG, UK.
Tulane National Primate Research Center, School of Medicine, Tulane University, Covington, GA 70433, USA.
Vaccines (Basel). 2022 Jan 25;10(2):187. doi: 10.3390/vaccines10020187.
Non-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured systemically. We assessed the mucosal responses elicited upon vaccination with ALVAC and AIDSVAX using ex vivo Rhesus macaque mucosal tissue explant models. Following booster immunization with ALVAC/AIDSVAX, anti-gp120 HIV-1-specific IgG and IgA were detected in culture supernatant cervicovaginal and colorectal tissue explants, as well as systemically. Despite protection from ex vivo viral challenge, no neutralization was observed with tissue explant culture supernatants. Priming with ALVAC induced distinct cytokine profiles in cervical and rectal tissue. However, ALVAC/AIDSVAX boosts resulted in similar modulations in both mucosal tissues with a statistically significant decrease in cytokines linked to inflammatory responses and lymphocyte differentiation. With ALVAC/AIDSVAX boosts, significant correlations were observed between cytokine levels and specific IgA in cervical explants and specific IgG and IgA in rectal tissue. The cytokine secretome revealed differences between vaccination with ALVAC and ALVAC/AIDSVAX not previously observed in mucosal tissues and distinct from the systemic response, which could represent a biosignature of the vaccine combination.
非人灵长类动物（NHPs）仍然是评估HIV疫苗候选物最相关的挑战模型；然而，与临床试验结果的差异强调了进一步完善非人灵长类动物模型的必要性。此外，对疫苗候选物的经典评估基于全身测量的终点指标。我们使用恒河猴黏膜组织外植体模型评估了接种ALVAC和AIDSVAX后引发的黏膜反应。用ALVAC/AIDSVAX加强免疫后，在宫颈阴道和结直肠组织外植体的培养上清液以及全身均检测到抗gp120 HIV-1特异性IgG和IgA。尽管能在体外保护免受病毒攻击，但组织外植体培养上清液未观察到中和作用。用ALVAC进行初免在宫颈和直肠组织中诱导了不同的细胞因子谱。然而，ALVAC/AIDSVAX加强免疫在两个黏膜组织中导致了类似的调节，与炎症反应和淋巴细胞分化相关的细胞因子有统计学意义的下降。在进行ALVAC/AIDSVAX加强免疫后，在宫颈外植体中细胞因子水平与特异性IgA之间以及在直肠组织中特异性IgG和IgA之间观察到显著相关性。细胞因子分泌组揭示了接种ALVAC和ALVAC/AIDSVAX之间在黏膜组织中以前未观察到的差异，且不同于全身反应，这可能代表了该疫苗组合的生物特征。
