This randomized pilot phase II trial studies how well vaccine therapy works in treating human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells.

PRIMARY OBJECTIVES:

I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma > 1 mm thick.

II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide.

III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.

IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune).

V. To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide.

VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the second vaccination. Patients with positive lymph nodes undergo complete lymph node dissection and resume vaccinations.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Inclusion Criteria:

• Patients must have histologically confirmed primary melanoma of Breslow thickness 1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however, those who have already undergone a wide local excision are also eligible; patients may be enrolled up to three months after their wide local excision
• Patients whose melanoma is > 4.0 mm thick who have positive or negative regional lymph nodes are also eligible
• After accrual to the original 26 patient goal, all patients must be enrolled prior to sentinel lymph node dissection; patients with previous lymph node dissection will not be eligible
• Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic techniques, flow cytometry, or molecular techniques
• Patients must be ambulatory with good performance status (Karnofsky performance status [PS] 80-100)
• White blood cell (WBC) >= 3500/mm^3
• Platelets (Plt) >= 100,000/mm^3
• Hemoglobin >= 9 gm/100 ml
• Serum creatinine =< 2 mg/dl
• Total bilirubin =< 2.0 mg/dl
• Patients must have recovered from any effects of major surgery and be free of significant systemic infection
• Patients must be negative for human immunodeficiency virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) (or negative by Western blot if ELISA is positive) if they are considered to be at high risk; others do not require serologic testing if there are no symptoms or risk factors for HIV disease
• Women of childbearing potential must have a negative pregnancy test and should avoid becoming pregnant while on treatment
• Patients must give written informed consent prior to initiation of therapy; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy

Exclusion Criteria:

• Patients must not have clinically detectable distant metastases
• Patients who require or are likely to require systemic corticosteroids for intercurrent illness
• Patients with any significant medical disease other than the malignancy (e.g. chronic obstructive pulmonary disorder [COPD], patients with ascites or pleural effusions) which in the opinion of the investigator would significantly increase the risk of immunotherapy
• Patient should be free of any other cancers or deemed at low risk for their recurrence