Inclusion Criteria:  Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the MSK Department of Pathology) or BM metastases plus high urine catecholamine levels.  Note: Bone Marrow aspirates must be done at the MSK Department of Pathology for patient enrollment onto the protocol  HR-NB as defined by risk-related treatment guidelines and international criteria,i.e., metastatic/non-localized disease with MYCN amplification (any age), MYCN-non-amplified metastatic disease >18 months old, MYCNamplified localized disease (any age), or disease resistant to standard chemotherapy. HR-NB (as defined above) and in 1) first CR at ≥ 6 months from initiation of immunotherapy using anti-GD2 antibody, or 2) second or subsequent CR (achieved after treatment for PD). CR is defined according to the International Neuroblastoma Response Criteria.Patients with positive MIBG scan but negative FDG-PET scan, and CR in BM, are eligible. Patients with grade 3 toxicities or less using the Common Toxicity Criteria (Version 5.0) developed by the National Cancer Institute of the USA (CTCAE v5.0) related to hematologic, cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam.  Hematologic Function  Absolute neutrophil count (ANC) ≥ 500/mcl Absolute lymphocyte count ≥ 500/mcl Hemaglobin (Hgb) ≥ 8 g/dL Platelet count ≥ 50,000 mm^3 Renal Function o Serum creatinine ≤ 3.0 x ULN  or  eGFR >60 mL/min/1.73 m^2  - Hepatic Function  Serum bilirubin ≤ 3.0 × ULN Aspartate transaminase (AST) ≤ 5.0 × ULN  Alanine aminotransferase (ALT) ≤ 5.0 × ULN  Prior treatment with other immunotherapy, including mAbs or vaccine, is allowed but must be completed ≥ 21 days before the 1st vaccination.  Note: Prior treatment with an investigational therapy must be completed ≥ 28 days before the 1st vaccination.  ≥ 21 and ≤ 180 days between completion of systemic therapy and 1st vaccination. Patients have recovered from any toxicities grade 3 or higher caused by prior therapies. Patients with history of allergy to GM-CSF or who are unable to obtain GM-CSF because of insurance issues are eligible but will be assigned to Group 3 (no GM-CSF exploratory arm). Patients previously enrolled on this trial are eligible for repeat enrollment if they did not complete all vaccine injections during the first time on protocol but they will be assigned to Group 3 and will not be included in the primary biostatistical analyses. A negative pregnancy test is required for patients w ith child-bearing capability. Signed informed consent indicating awareness of the investigational nature of this program.  Exclusion Criteria:  Patients w ith significant (grade >4) hematologic, cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam, using the Common Toxicity Criteria (Version 5.0) developed by the National Cancer Institute of the USA (CTCAE v5.0) History of allergy to KLH, QS-21, OPT-821, or glucan. Active life-threatening infection requiring systemic therapy. Inability to comply with protocol requirements.