Görkem YAMAN, Mustafa BERKTAŞ, HÜSEYİN GÜDÜCÜOĞLU

Tartışılan adjuvan: Skualen

2009 yılında pandemik influenza A H1N1 virüsüne bağlı olarak ortaya çıkan salgında en etkili korunma yönteminin aşılanma olduğu vurgulanmasına rağmen, özellikle aşı içeriğinde bulunan skualen ve oluşturduğu yan etkiler konusundaki spekülasyonlar aşının etkinliğini gölgelemiş ve tartışmalara neden olmuştur. Terpenoidler içinde triterpen sınıfında yer alan doğal organik bir lipid olan skualen, biyolojik kökenli ve yıkılabilir bir yağ olması, besin takviyesi olarak ya da kozmetik endüst ri alanında sıkça kullanılması yanında tedavi uygulamalarında su içi yağ emülsiyonu şeklinde aşı adjuvanı olarak da kulla nılmaktadır. İnfluenza aşı içeriğinde yer alan skualenin tween 80 ve span 85 ile beraber oluşturulan formülasyonlarının, güçlü hümoral yanıt dışında, hücresel tipte bağışıklık yanıtı da uyardığı ve etkisinin uzun zamandır kullanılan bir adjuvan olan alum’a göre daha güçlü ve uzun süreli olduğu saptanmıştır. Skualenin yan etkileri üzerinde yapılan çalışmalarda yerel ve kısa süreli yan etkilerinin adjuvansız aşılara göre daha yüksek oranlarda saptanmasına rağmen, beklenmedik veya ciddi yan etkiler açısından anlamlı farklar bulunamamıştır. Körfez savaşı harekâtına katılan askerlerde görülen kronik multisemptomatik hastalık (Körfez savaşı sendromu) etiyo lojisinde o dönem yapılan aşıların skualen içermesi ve hastalık ile anti-skualen antikorlar arasında anlamlı bir ilişki bulundu ğu raporlanmasına karşın, bu yayınların yeterliliği ve kullanılan yöntemlerin güvenilirliği ciddi şekilde tartışılmıştır. Son dönemde onaylanmış yöntemler ve kontrol grupları kullanılarak yapılan yayınlar sonucunda, skualen antikorları ve hastalık arasında var olduğu iddia edilen bu ilişki doğrulanamamıştır. Bu derlemede, aşı uygulamaları yanında ilaç ve gen transferi konularında da gelecek vaat eden skualen, literatür bilgi leri ışığında mercek altına alınmıştır.

Anahtar Kelimeler:

Grip aşıları, Influenza A virüsü, Skualen, İnfluenza A virüsü, H1N1 tipi

Squalene: The controversial adjuvant

Although influenza vaccination is announced to be the most effective prevention method for the outbreak of 2009 pan demic influenza A H1N1 virus, especially the speculations for vaccine ingredient squalene and its adverse effects have supp ressed its effectiveness and caused controversy. Squalene, a natural organic lipid which belongs to triterpene class of terpeno ids, is used for medical purposes, besides dietary supplement and in cosmetics industry, as oil-in-water emulsion vaccine adjuvant because of being degradable oil and its biological origin. Formulations of squalene with tween 80 and span 85 which are ingredients of influenza vaccines, have proved to indu ce potent humoral responses as well as cellular immune responses and their effectiveness to be more potent and long lasting than alum which is an adjuvant used in vaccines for more than 70 years. In a series of studies on adverse effects of squalene, although local and short term adverse effects were detected to be more frequent compared to non-adjuvanted vaccines, there were no significant differences in terms of unexpected or serious adverse effects. After it was reported that squalene was included in multi-vaccination program and there was a significant correlation with anti-squalene antibodies and chronic multisymptomatic illnesses (Gulf war syndrome) in American veterans during the Gulf war, the adequacy of these reports and validations of the performed methods were extensively questioned. As a result of recent reports using validated methods and control groups, the claimed correlation between squalene antibodies and the illness could not be confirmed. In this review, squalene which has a bright future in drug and gene transfer as well as vaccine applications is examined into with the light of recent publications.

Keywords:

Influenza Vaccines, Influenza A virus, Squalene, Influenza A Virus, H1N1 Subtype,

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