An investigational human papillomavirus ( HPV ) 16/18 L1 vaccine formulated with an innovative adjuvant, AS04, induced a stronger immune response, when compared to the same vaccine formulated with aluminum salt alone.
This stronger response was sustained over 3.5 years post vaccination in women.

These results, based on three separate assessments, including in-vitro evaluation of biological activity of AS04, production of anti-HPV 16 and HPV 18 antibodies and inhibition of major neutralizing epitopes in animal and human subjects, were presented at the American Association for Cancer Research ( AACR ) International Conference on Frontiers in Cancer Prevention Research in Baltimore.

HPV is the leading cause of cervical cancer. Seventy percent ( 70% ) of all cervical cancer cases are associated with only two oncogenic types, HPV 16 and HPV 18.
GlaxoSmithKline’s cervical cancer vaccine candidate targeting these two oncogenic HPV types is currently undergoing Phase III clinical trials involving more than 28,000 women worldwide.

Three separate methods were used to evaluate the ability of an HPV 16/18 L1 VLP vaccine formulated with either the AS04 adjuvant, composed of aluminum plus 3-deacylated monophosphoryl lipid A ( MPLTM ), or aluminum salt alone to induce an immune response of high magnitude and persistence.

The first assessment was carried out in culture cells. Activation of the immune system by AS04 or aluminum salt alone was assessed in-vitro using the human monocyte cell line U937. Using a common immunology test, ELISA ( Enzyme-Linked Immunosorbent Assay ), researchers evaluated the production of TNFa ( Tumor Necrosis Factor-alpha ).
Data demonstrate that AS04 was associated with substantial and greater induction of TNFa production, compared to aluminum salt alone.

In addition, following vaccination with an HPV 16/18 L1 vaccine of subjects including women aged 18 to 30, serum samples were evaluated for antibodies to HPV 16 and HPV 18 L1 VLPs. Furthermore, an inhibition ELISA was used for measure of antibodies specifically directed against the major neutralizing sites on HPV 16 and HPV 18, known as V5 and J4 epitopes, respectively.
The findings demonstrate that one month following the second or third vaccine doses, GlaxoSmithKline’s investigational cervical cancer vaccine formulated with AS04 induced anti-VLP16 and 18 antibodies that were substantially higher than with the aluminum salt only formulation.
Additionally, higher levels of antibodies directed against key V4 and J5 neutralizing epitopes were induced. Moreover, the higher antibody responses associated with the AS04 formulation persisted for up to at least 3.5 years post-vaccination in human subjects.

The overall safety profile from the completed controlled trials indicate that the vaccine is generally safe and well tolerated with a very good compliance to the 3 dose schedule.

Cervical cancer is a major global health problem, with nearly 500,000 new cases occurring each year worldwide.
It is the second most common cancer – and the third leading cause of cancer deaths – in women worldwide.
Each year an estimated 270,000 women die from the disease, and it is the leading cancer killer of women in the developing world. HPV is the leading cause of cervical cancer.
There are many types of HPV; however, 70 percent of all cervical cancer cases are associated with only two oncogenic types, HPV 16 and HPV 18.

HPV infection is very common among sexually active people, and in fact, it is estimated that by the age of 50, approximately 80 percent of women will have been infected with HPV. Genital HPV infection is especially common in women under the age of 25. HPV infections are usually transient and generally cause no symptoms. Persistent infection with oncogenic types of HPV may lead to cervical cancer.

Source: GlaxoSmithKline, 2005


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