Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251.
Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251.
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DOI：
10.1038/s41467-023-36907-0
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发表时间：
2023-03-07
影响因子：
16.6
通讯作者：
Mattapallil, Joseph J.
中科院分区：
文献类型：
--
作者：
Mattathil, Jeffy G.;Volz, Asisa;Onabajo, Olusegun O.;Maynard, Sean;Bixler, Sandra L.;Shen, Xiaoying X.;Vargas-Inchaustegui, Diego;Robert-Guroff, Marjorie;Lebranche, Celia;Tomaras, Georgia;Montefiori, David;Sutter, Gerd;Mattapallil, Joseph J.
人类免疫缺陷病毒（HIV）是一种引起免疫缺陷和艾滋病的粘膜传播病毒。研制有效的疫苗预防感染对控制疫情至关重要。鉴于粘膜和外周免疫系统之间存在显著的区隔性，保护阴道和直肠粘膜，HIV进入的主要途径一直是一项挑战。我们假设直接在结内接种粘膜相关淋巴组织（MALT），如容易接近的腭扁桃体，可以克服这种区隔化。在这里，我们发现用编码SIVmac251-env和gag基因的质粒DNA启动恒河猴，然后用编码相同基因的MVA在结内扁桃体MALT增强，保护恒河猴免受高致病性SIVmac251的重复低剂量直肠内攻击；与未接种疫苗的对照动物（0/6）相比，43%（3/7）接种疫苗的猕猴在9次攻击后仍未被感染。一只接种过疫苗的动物即使在22次挑战后仍未被感染。接种疫苗与急性病毒血症降低约2个对数相关，与遗忘性免疫反应呈负相关。我们的研究结果表明，全身性和结内扁桃体MALT疫苗联合接种可以诱导强大的适应性和先天免疫反应，从而保护机体免受高致病性HIV的粘膜感染，并迅速控制病毒的突破。粘膜表面是HIV进入的主要途径，然而粘膜和外周免疫系统之间的区隔化仍然是HIV候选疫苗的一个挑战。作者在恒河猴模型中利用结内扁桃体MALT和全身疫苗接种的组合来探索免疫应答和对高致病性HIV同源猿类的保护。
Human immunodeficiency virus (HIV) is a mucosally transmitted virus that causes immunodeficiency and AIDS. Developing efficacious vaccines to prevent infection is essential to control the epidemic. Protecting the vaginal and rectal mucosa, the primary routes of HIV entry has been a challenge given the significant compartmentalization between the mucosal and peripheral immune systems. We hypothesized that direct intranodal vaccination of mucosa associated lymphoid tissue (MALT) such as the readily accessible palatine tonsils could overcome this compartmentalization. Here we show that rhesus macaques primed with plasmid DNA encoding SIVmac251-env and gag genes followed by an intranodal tonsil MALT boost with MVA encoding the same genes protects from a repeated low dose intrarectal challenge with highly pathogenic SIVmac251; 43% (3/7) of vaccinated macaques remained uninfected after 9 challenges as compared to the unvaccinated control (0/6) animals. One vaccinated animal remained free of infection even after 22 challenges. Vaccination was associated with a ~2 log decrease in acute viremia that inversely correlated with anamnestic immune responses. Our results suggest that a combination of systemic and intranodal tonsil MALT vaccination could induce robust adaptive and innate immune responses leading to protection from mucosal infection with highly pathogenic HIV and rapidly control viral breakthroughs. Mucosal surfaces are a primary route of HIV entry, yet the compartmentalisation between mucosal and peripheral immune systems remain a challenge for HIV vaccine candidates. Authors utilise a combination of intranodal tonsil MALT and systemic vaccination in the rhesus macaque model to explore immune responses and protection from highly pathogenic simian homologue of HIV.
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影响因子：
7.3
作者：
Velarde de la Cruz E;Wang L;Bose D;Gangadhara S;Wilson RL;Amara RR;Kozlowski PA;Aldovini A
通讯作者：
Aldovini A
影响因子：
7.2
作者：
Bol KF;Figdor CG;Aarntzen EH;Welzen ME;van Rossum MM;Blokx WA;van de Rakt MW;Scharenborg NM;de Boer AJ;Pots JM;Olde Nordkamp MA;van Oorschot TG;Mus RD;Croockewit SA;Jacobs JF;Schuler G;Neyns B;Austyn JM;Punt CJ;Schreibelt G;de Vries IJ
通讯作者：
de Vries IJ
影响因子：
3.7
作者：
Harmon TM;Fisher KA;McGlynn MG;Stover J;Warren MJ;Teng Y;Näveke A
通讯作者：
Näveke A
影响因子：
4.6
作者：
George J;Valiant WG;Mattapallil MJ;Walker M;Huang YS;Vanlandingham DL;Misamore J;Greenhouse J;Weiss DE;Verthelyi D;Higgs S;Andersen H;Lewis MG;Mattapallil JJ
通讯作者：
Mattapallil JJ
影响因子：
3.7
作者：
Gasper MA;Biswas SP;Fisher BS;Ehnert SC;Sherman DR;Sodora DL
通讯作者：
Sodora DL