Therapeutic HPV DNA vaccines

Abstract

It is now well established that most cervical cancers are causally associated with HPV infection. This realization has led to efforts to control HPV-associated malignancy through prevention or treatment of HPV infection. Currently, commercially available HPV vaccines are not designed to control established HPV infection and associated premalignant and malignant lesions. To treat and eradicate pre-existing HPV infections and associated lesions which remain prevalent in the U.S. and worldwide, effective therapeutic HPV vaccines are needed. DNA vaccination has emerged as a particularly promising form of therapeutic HPV vaccines due to its safety, stability and ability to induce antigen-specific immunity. This review focuses on improving the potency of therapeutic HPV vaccines through modification of dendritic cells (DCs) by [1] increasing the number of antigen-expressing/antigen-loaded DCs, [2] improving HPV antigen expression, processing and presentation in DCs, and [3] enhancing DC and T cell interaction. Continued improvement in therapeutic HPV DNA vaccines may ultimately lead to an effective DNA vaccine for the treatment of HPV-associated malignancies.

Induction of robust cellular immunity against HPV6 and HPV11 in mice by DNA vaccine encoding for E6/E7 antigen

“…and combinations of different vaccine platforms, targeting HPV oncogenes. [8][9][10][11] Recent discoveries from such research have shed light on the growing promise of DNA-based vaccines as a possible therapeutic approach against HPV. DNA vaccines contain antigen-specific genes that are later expressed and presented to lymphocytes by antigen-presenting cells (APCs), such as dendritic cells.…”

“…Numerous optimization, delivery and boost strategies have been developed and are currently being studied. 8,[12][13][14][15][16][17][18] Recent work on DNA vaccines for HPV therapy have produced promising preliminary results which have now led to clinical trials targeting the HPV 16 or 18 subtypes. [12][13][14][19][20][21][22] However, there have been no prior reports focusing on HPV subtypes 6 + 11.…”

HPV vaccine: Current status and future directions

“…The possibility of vaccine resistance by development of vector specific antibodies or by a pre-existing vector-specific immunity thus making the vaccine potentially ineffective needs to be addressed. 28,29 Bacterial vector based vaccine Many bacteria have been studied as vectors for HPV immunization. One of which, the Listeria monocytogenes, invades macrophages and evades phagocytosis within the phagosome by using Listeriolysin O (LLO) a pore forming toxin, can successfully deliver the antigen into cytoplasm and in turn activate CD8þ cytotoxic cells and CD4þ T helper cells finally creating cell mediated immunity and is being tried as ADXS II-001, a live attenuated Listeria based HPV 16 E7 vaccine on patients with HPV associated oropharyngeal cancers, cervical cancers and CIN 2/3.…”

“…One of which, the Listeria monocytogenes, invades macrophages and evades phagocytosis within the phagosome by using Listeriolysin O (LLO) a pore forming toxin, can successfully deliver the antigen into cytoplasm and in turn activate CD8þ cytotoxic cells and CD4þ T helper cells finally creating cell mediated immunity and is being tried as ADXS II-001, a live attenuated Listeria based HPV 16 E7 vaccine on patients with HPV associated oropharyngeal cancers, cervical cancers and CIN 2/3. 28 Lactobacillus casei and Lactobacillus lactis also has been tried as bacterial vectors. …”

“…pnGVL4a-CRT/E7 (detox) is a therapeutic DNA vaccine undergoing phase II trial for treating CIN2/3 lesions. 26,28,29 Dendritic cell based vaccines Dendritic cells are the dedicated antigen presenting cells in the body which induce T cell response through MHC eI and II pathways. 'Pulsing' dendritic cells with HPV antigens or peptides or DNA encoding the antigens in vivo enables loading of the MHC I and II molecules with HPV epitopes.…”