Vaccine Therapy in Healthy Volunteers With or Without Previous Exposure to Cytomegalovirus

Inclusion Criteria: * Sodium range from within normal institutional limits to less than a grade I toxicity * Potassium range from within normal institutional limits to less than a grade I toxicity * Chloride range from within normal institutional limits to less than a grade I toxicity * Carbon dioxide range from within normal institutional limits to less than a grade I toxicity * Glucose range from within normal institutional limits to less than a grade I toxicity * Alkaline phosphatase (AP) range from within normal institutional limits to less than a grade I toxicity * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) range from within normal institutional limits to less than a grade I toxicity * Blood urea nitrogen (BUN) range from within normal institutional limits to less than a grade I toxicity * Creatinine range from within normal institutional limits to less than a grade I toxicity * Lactic dehydrogenase (LDH) range from within normal institutional limits to less than a grade I toxicity * Total bilirubin range from within normal institutional limits to less than a grade I toxicity * Uric acid range from within normal institutional limits to less than a grade I toxicity * Albumin \> lower limit of normal institutional limits * White blood count range from within normal institutional limits to less than a grade I toxicity * Hemoglobin (HGB) range from within normal institutional limits to less than a grade I toxicity * Hematocrit (HCT) range from within normal institutional limits to less than a grade I toxicity * Platelet count is within the lower limit of normal institutional limits and not more than 1.5 times the upper limit of normal institutional limits * Hepatitis B virus (HBV) surface antigen negative and hepatitis C virus (HCV) seronegative; human immunodeficiency virus (HIV)-1 seronegative * Currently not taking daily medications for chronic or intercurrent illness; those medications which are excepted from this rule are thyroid replacement, estrogen replacement, dietary vitamins and protein supplements, and any medications not known or likely to be immunosuppressive, as determined by the principal investigator (PI) * No surgery in past 6 months which required general anesthesia, but minor procedures, such as dental surgery and superficial diagnostic biopsies, are permitted * No diagnosis which has been associated with immunodeficiency * No active infection for which the subject is receiving treatment * Framingham Risk Score for cardiovascular disease =\< 10%; no history of heart disease, e.g. previous treated arrhythmia or myocardial infarction; no horizontal positioning-induced or activities of normal living exercise-induced shortness of breath; no history of stroke or claudication; no current treatment with medication for high cholesterol or other lipid abnormality; a documented electrocardiogram (ECG) and cardiac troponin must be within normal institutional limits in the past 30 days; "normal ECG with sinus tachycardia" or " normal ECG with sinus bradycardia" is allowable based on a history of absent cardiac/exercise related symptoms as determined by the P.I. in consultation with a senior staff cardiologist * No history of or prior treatment for diabetes type 1 or diabetes type 2 * Women of childbearing age must have a negative urine pregnancy test and must not be planning to become pregnant within the next 6 months * No history of adverse events with a prior smallpox vaccination SECONDARY ELIGIBILITY CRITERIA: * It is anticipated that there could be a delay of 1-3 months between screening and actual vaccination; alternatively, there could be a delay due to availability of the vaccine; therefore, prior to registration for vaccination, the following secondary eligibility criteria must be met: * If not tested in past 4 months, serum chemistries and blood counts are within normal limits; hepatitis B virus (HBV) surface antigen negative and hepatitis C virus (HCV) seronegative; HIV-1 antibody negative * Women of childbearing age must have a urine pregnancy test performed within 48 hours of each vaccine administration with a negative result * Laboratory values prior to booster injection may include grade 1 laboratory abnormalities, but any grade \>= grade 2 will exclude the subject from a booster injection Exclusion Criteria: * Any previous condition, or one that becomes known during the screening period, that would suggest that the individual could be immunologically impaired, or for which this study would pose a danger to him/herself or about which the P.I., in evaluating the subject for eligibility, determines that this exclusion is appropriate * Subjects are excluded who have a history of cancer other than basal cell skin cancer, or any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc. as determined by the PI. In addition, allergic diatheses as define by a history of asthma, anaphylaxis, or generalized urticaria, or by daily use of antihistamines, episodic (more than once in past 3 months) inhalational medications including steroidal agents, non-steroidal agents, or cromolyn sodium * Subjects with severe migraine headaches (more than one per month on average in the past 6 months or requiring preventive medications) are excluded * Any of the following cardiac findings of ECG abnormality: * Conduction disturbance (complete left or right bundle branch block, intraventricular conduction disturbance with QRS \> 120 ms, atrioventricular block \[AV\] block of any degree, and corrected QT \[QTc\] prolongation \> 450 msec for men and \> 460 msec for women) * Repolarization (ST segment or T wave) abnormality * Significant atrial or ventricular arrhythmia, including frequent ectopy (e.g., 2 premature ventricular contractions in a row; and * Evidence of past myocardial infarction * Any previous condition, or one that becomes known during the screening period, that would suggest that the technicians and health professionals involved in the study would be exposed to specific infectious risk * Treatment with whole or subunit CMV or poxvirus vaccine in the last 12 months * Men with partners of child-bearing potential and women of child-bearing potential who are not willing to use medically effective birth control methods, e.g. contraceptive pill, condom, or diaphragm, and continue this for 6 weeks after the second and last dose of vaccine * Subjects who have had a live vaccine =\< 30 days prior to administration of study vaccine or subjects who are =\< 2 weeks within administration of inactivated vaccines (e.g. influenza vaccine) * Persons who are employed by or are a student at City of Hope and are in a chain of command that reports directly to persons listed on the protocol as Principal Investigator or Co-Investigator.