Vaccine Therapy and Resiquimod in Treating Patients With Stage II-IV Melanoma That Has Been Removed By Surgery

Inclusion Criteria: * Central pathology review submission; this review for MART-1 positivity is mandatory prior to registration to confirm eligibility * Human leukocyte antigen (HLA)-A2-positive * Histologic proof of stage II, III or IV melanoma that has been completely resected with no current evidence of disease, as demonstrated by imaging within 2 months (stage III or stage IV; must be computed tomography \[CT\], magnetic resonance imaging \[MRI\], or positron emission tomography \[PET\]/CT) or 6 months (stage II; may be chest x-ray, CT, MRI, or PET/CT) * Absolute neutrophil count (ANC) \>= 1500 mL * Hemoglobin (Hgb) \> 10 g/dL * Platelets (PLT) \>= 50,000 mL * Aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN) * Alkaline phosphatase =\< 3 x ULN * Ability to provide informed consent * Willingness to return to Mayo Clinic Rochester for follow-up * Life expectancy \>= 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 * For women of childbearing potential, a negative serum pregnancy test =\< 7 days prior to registration * Willingness to provide mandatory blood samples for correlative research Exclusion Criteria: * Uncontrolled or current infection * Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy * Known allergy to vaccine or adjuvant components * Any of the following prior therapies with interval since most recent treatment: * Chemotherapy =\< 4 weeks prior to registration * Biologic therapy or immunotherapy =\< 4 weeks prior to registration * Radiation therapy =\< 4 weeks prior to registration * Failure to fully recover from side effects of prior chemotherapy or surgery * Any of the following, as this regimen may be harmful to a developing fetus or nursing child: * Pregnant women * Nursing women * Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) * Known immune deficiency, including human immunodeficiency virus (HIV) infection, as patients with known immune deficiencies will likely not be able to mount an immune response to the study vaccine; in addition, study patients should be naive to the HIV-derived Gag267-274 antigen * History of systemic autoimmune disease, as patients with ongoing autoimmunity may be at an increased risk of autoimmune toxicity from the study vaccine * Current or recent (=\< 4 weeks prior to registration) use of immunosuppressive medications including systemic corticosteroids; (use of corticosteroids in doses not exceeding those used for adrenal replacement is acceptable) * History of brain metastases (even if completely resected) * Other active malignancy =\< 5 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other treatment for their cancer