Cervicovaginal Immune Responses to 3 Deltoid or Thigh Intramuscular (IM) TicoVac

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

Many viral infections of global importance, including HIV, are transmitted across the mucosal surface of the genital tract. As immunity against these infections is likely to be primarily mediated by antibodies in mucosal secretions, developing techniques to increase the levels and persistence of antiviral antibody on mucosal surfaces may enhance the protection against a number of important infections. Preclinical studies have anatomically targeted vaccine antigens to sites where genital tract immunity is induced. This response is likely due to the ability of regional lymph Preclinical studies have anatomically targeted vaccine antigens to sites where genital tract immunity is induced. This response is likely due to the ability of regional lymph nodes to "pattern" the cell surface markers of responding vaccine specific lymphocytes with homing markers. In contrast, injecting a distant muscle (such as in the arm) which shares no anatomical relationship with the vagina, may not pattern cells with homing markers for the genital tract. Direct injection of inguinal lymph nodes is impractical in humans but intramuscular injection into the thigh will target antigens to the deep inguinal lymph nodes shared in common with the cervix/vagina.

This study will be a Phase IV randomised, single centre, open label, laboratory assessment blinded exploratory trial to assess mucosal immunogenicity following three targeted intramuscular immunisations with TicoVac vaccine. 20 subjects will be randomised to each of2 groups immunised in right deltoid or right anterolateral thigh.

Following an initial screening visit subjects will be immunised at 0, 1 and 6 months. There will be follow up visits 5 days after each immunisation and a final visit at 7 months. Blood samples and cervicovaginal secretions will be taken prior to each immunisation for immunological measures. In addition, blood samples will be taken at each immunisation and follow up visit for measurement of peripheral blood mononuclear cells.

The study is funded by ADITEC, which is a collaborative research programme that aims to accelerate the development of novel and powerful immunisation technologies for the next generation of human vaccines.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Surrey
• Treatments: Vaccines

Criteria

Inclusion criteria

• Women aged between 18 and 49 years on the day of screening.

• Available for follow-up for the duration of the study.

• Willing and able to give written informed consent.

• Agree to abstain from donating blood during and for three months after the end of their participation in the trial, or longer if necessary.

• Willing to abstain from vaginal intercourse for 12 hours prior to cervico-vaginal secretions sampling.

Exclusion criteria

• Previous immunisation with a TBEV vaccine or history of TBEV infection.

• Previous immunisation with a Yellow Fever or Japanese B encephalitis vaccine, or history of infection with Yellow fever, Japanese B encephalitis, hepatitis C and dengue infection (as antibodies against these viruses cross react with TBE). Immunisation with Yellow Fever or Japanese B encephalitis vaccine or diagnosis of any of these infections during the study period will exclude the subject.

• Intention to travel to an area requiring immunisation against Japanese B encephalitis within 40 days and yellow fever within 10 days of the expected last visit(as Japanese B encephalitis vaccine requires two immunisations 28 days apart and must be completed within 10 days of departure. Yellow Fever vaccination becomes effective 10 days after a single immunisation)

• Any Intra Uterine Contraceptive Device (as this contraindicates with use of the Softcup).

• Pregnant or lactating at time of screening or immunisations.

• Known hypersensitivity to the vaccine active substance, any of the excipients, or the production residues (formaldehyde, neomycin, gentamicin, protamine sulphate).

• Latex allergy.

• Severe hypersensitivity to egg and chick proteins ("severe" means anaphylactic reaction after oral ingestion of egg protein - other reactions are not exclusions).

• Clinically relevant abnormality on history including uncontrolled infection; autoimmune disease, immunodeficiency, or pre-existing cerebral disorders.

• Any drugs and categories of drugs listed in Appendix 1, by the routes indicated, and at any time during the study period, or for the period preceding screening indicated in Appendix 1.

Any medications that are not listed in Appendix 1,or any over-the-counter treatments are not excluded.

Receipt of vaccines other than TBEV vaccines is not excluded. If other injectable vaccines are to be given during the study period, administration should preferably be into different limbs from the study vaccine.

• Receipt of blood products or immunoglobin within 3 months of screening.

• Participation in another trial of a medicinal product, completed less than 90 days prior to visit 2.

• Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.

• Unlikely to comply with protocol.