Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine

Abstract

Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico, a women dies every 2 h, and since 1990 the statistics have shown that the numbers of deaths are increasing. We conducted a phase II clinical trial to evaluate the potential use of the MVA E2 recombinant vaccinia virus in treating high-grade lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four female patients with high degree lesions were treated either with an MVA E2 therapeutic vaccine or with conization. Thirty-four women received the therapeutic vaccine, at a total of 10 7 virus particles per dose injected directly into the uterus once every week over a 6-week period. Twenty control patients were treated with conization. By colposcopy, 19 patients out of 34 showed no lesion, in three patients the lesions were reduced by 85-90%, in eight other lesions had reduced by 60%, and in four more patients, they were reduced by 25%. Histological analysis showed total elimination of high-grade lesions in 20 out of 34 patients after treatment with MVA E2. Eleven patients had a 50% reduction in lesion size. In two other patients, the lesion was reduced to CIN 2 and in one more patient the lesion was reduced to low grade (CIN 1). All patients developed antibodies against the MVA E2 vaccine, and generated a specific cytotoxic response against papilloma-transformed cells. DNA viral load was significantly reduced in MVA E2-treated patients. Conization eliminated the lesions in 80% of the patients, but patients did not develop cytotoxic activity specific against cancer cells and did not eliminate the papillomavirus. In addition, three patients treated with conization had recurrence of lesions 1 year later. These results show that therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of high-grade lesion.

Therapeutic vaccination of rabbits with a ubiquitin-fused papillomavirus E1, E2, E6 and E7 DNA vaccine

“…However, when brought to clinical trials, such vaccines have provided little if any clinical benefit to human patients [16][17][18][19][20][21][22][23]. These findings indicate the need for more faithful preclinical models of high risk HPV-associated disease.…”

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

“…In earlier studies, dogs, immunized against papilloma E1 and E2 proteins, did not show papilloma growth after viral challenge, or even presented complete regression of papilloma [88,89]. [90,91]. As indicated before, the E6 and E7 proteins are important for cancer.…”

Recent advances in strategies for immunotherapy of human papillomavirus‐induced lesions

“…The clinical trials targeting the E2 protein in patients with CIN2/3 or genital warts have reported significant promise in terms of clinical responses. 21,22 However, due to the lack of controls, it is not clear whether some of the clinical responses are due to (i) natural spontaneous regression of the lesions, (ii) the local delivery route of the vaccine (intrauteral/ intraurethral), (iii) the choice of the antigen (bovine papillomavirus (BPV) E2) or (iv) the immune-stimulatory adjuvant effects of repeated viral delivery with MVA. In addition, the rationale for vaccinating against the E2 protein from BPV instead of an HPV genotype is not clear, though it is theoretically possible that the patient's immune system is tolerized against HPV E2, but can still respond to epitopes derived from BPV E2.…”