Phase I Evaluation of a CMV-MVA Triplex Vaccine: Safety and Biologically Effective Dose in Healthy Volunteers With or Without Prior Immunity to CMV and Vaccinia
Phase I Evaluation of a CMV-MVA Triplex Vaccine: Safety and Biologically Effective Dose in Healthy Volunteers With or Without Prior Immunity to CMV and Vaccinia
This phase I trial studies the side effects and the best dose of vaccine therapy in healthy volunteers with or without previous exposure to cytomegalovirus. Vaccines made from a gene-modified virus may help the body build an immune response and may help prevent cytomegalovirus infection.
PRIMARY OBJECTIVES:
I. To establish a biological optimal dose of the cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) Triplex vaccine (multi-CMV epitope modified vaccinia Ankara vaccine).
II. To determine if the vaccine is safe and well tolerated in healthy volunteers at these doses.
SECONDARY OBJECTIVES:
I. To provide preliminary evidence of CMV-MVA Triplex vaccine driven expansion of CMV-specific immune responses that would support further evaluation of this vaccine in hematopoietic cell transplantation (HCT) recipients.
II. To confer CMV-specific immunity to CMV-negative volunteers and to determine the duration of immune enhancement of CMV-specific cell mediated immunity (CMI) function up to 12 months following immunization of healthy volunteers.
OUTLINE: This is a dose-escalation study.
Participants receive multi-CMV epitope modified vaccinia Ankara vaccine intramuscularly (IM) followed by a booster injection 28 days later in the absence of unacceptable toxicity.
After completion of study treatment, participants are followed up for 12 months.
Inclusion Criteria:
SECONDARY ELIGIBILITY CRITERIA:
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:
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.