RNA-lipid Particle (RNA-LP) Vaccines for Recurrent/Progressive Medulloblastoma (MB)

Inclusion Criteria: * Age \> 3 and \</= 39 years. * Histologically confirmed or suspected recurrent/progressive MB in first or second relapse. * Patients must have received radiation therapy as part of prior therapy. * Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs). * Prior Therapy: Patients must have fully recovered from all acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately. * XRT/External Beam Irradiation, including Protons: ≥ 90 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis. * Other therapeutic clinical trials: ≥ 14 days after last dose of investigational agent, unless otherwise defined above. * Patients must not have received prior exposure to pp65-directed therapy or any RNA-LP therapy. * A diagnostic contrast-enhanced MRI of the brain and spine must be performed preoperatively, and diagnostic contrast-enhanced MRI of the area biopsied or resected must be performed postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment. Post-op MRI must be completed within 7 days after surgery. * Performance Score: Karnofsky ≥ 60 for participants \> 16 years of age and Lansky ≥ 60 for participants \< 16 years of age (See Appendix A) assessed within 2 weeks prior to enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Bone Marrow: d. ANC (Absolute neutrophil count) ≥ 1,000/μl (unsupported) e. Platelets ≥ 100/μl (unsupported for at least 7 days) f. Hemoglobin \> 8 g/dL (may be supported) * Renal: Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 * Hepatic: d. Bilirubin ≤ 3 times upper limit of institutional normal for age. e. SGPT (ALT) ≤ 5 times upper limit of institutional normal for age. f. SGOT (AST) ≤ 5 times upper limit of institutional normal for age. * Participants who are receiving systemically-administered steroids must be on a stable or decreasing dose for \>1 week prior to enrollment. The patient steroid dose should be no more than a dexamethasone-equivalent of 2.8 mg/m2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed. * Willing to take an antiepileptic medication such as levetiracetam for the duration of RNA-LP vaccinations * A legal parent/guardian or patient must be able to understand and be willing to sign a written informed consent document * For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment * WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug. * Males of child-fathering potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug. * Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. * Patients must be enrolled on PNOC COMP prior to enrollment on PNOC020 if PNOC COMP is open to accrual at the enrolling institution. Exclusion Criteria: * Diffuse intrinsic pontine glioma, brainstem diffuse midline glioma, or BRAFV600E+ * Bulky disease, defined as: * Tumor with evidence of clinically significant uncal herniation, midline shift, tonsillar herniation, or brainstem infiltration, or that shows significant mass effect in either brain or spine * Tumor with extensive and diffuse multilobular involvement (\>3 lobes) * Tumor with extracranial disease (with the exception of spinal metastases in Stratum 3) * Known HIV, Hepatitis B, or Hepatitis C seropositive. * Uncontrolled seizure disorder * History of myocarditis * Receipt of any live vaccine within 30 days prior to enrollment * Known active infection or immunosuppressive disease. * Participants with significant renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), pulmonary, hepatic or other organ dysfunction. * Severe or unstable concurrent medical conditions. * Women must not be pregnant or breast-feeding. * Participants who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to study entry. * Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations.