• Diagnosis of CLL as per IWCLL 2018 criteria

• Patient's CLL must have an unmutated immunoglobulin heavy chain variable (IGHV) region gene, defined as \< 2% mutated compared to germline.

• Patient must have had no history of CLL-directed therapy due to meeting IWCLL 2018 criteria; no present indication for treatment by iwCLL 2018 criteria; and in the opinion of the treating investigator be anticipated not to require CLL-directed treatment within the next 6 months.

• Patient must have measurable disease (absolute lymphocyte count \> 10K/uL or total white blood cell count ≥ 20K/uL of peripheral blood).

• Patient must have had at least two other absolute lymphocyte counts (ALC) measured since diagnosis of CLL that are at least 2 weeks apart and at least 2 months prior to the one used for initial registration.

• Age ≥ 18 years.

• ECOG performance status 0 or 1

• Participants must have normal organ and marrow function as defined below:

‣ total bilirubin within normal institutional limits

⁃ AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

⁃ absolute neutrophil count ≥1000 cells/μL

• The effects of NeoVax and poly-ICLC on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent of HCG) before entry onto the trial and within 7 days prior to start of study medication. It is the investigators' responsibility to repeat the pregnancy test should start of treatment be delayed.

• Female patients enrolled in the study, who are not free from menses for \>2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 4 weeks after the last dose of study therapy. Approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.

• Patient is agreeable to allow tumor (from peripheral blood) and normal tissue (from saliva) samples to be submitted for complete exome and transcriptome sequencing.

• Ability to understand and the willingness to sign a written informed consent document.

• At least 7 immunizing peptides can be designed.

• Continue to meet inclusion and exclusion criteria for Screening Registration.