The aim of this study is to demonstrate that a single dose of rabies vaccine can induce an equally rapid and adequate anamnestic antibody response as 2-dose PrEP to revaccination six months later.
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the rate of increase of geometric mean concentrations
(GMC) of neutralizing antibodies between day 0 and day 7 after revaccination
for the different study groups.
Secondary outcome
Risk perception, knowledge and health beliefs concerning animal bites, animal
associated injuries and rabies
Attitudes towards rabies vaccination
Percentage of travellers with RVNA titer >0.5 IU/mL at day 0, 2 months, and six
months after primary vaccination. Percentage of travellers with RVNA titers>0.5
IU/mL at day 3, after the simulated post-exposure vaccination. Percentage of
travellers with RVNA titers>3 IU/mL, and percentage of travellers with RVNA
titers >5 IU/mL at day 7 after simulated PEP.
Which cellular and humoral immune responses are associated with an adequate
anamnestic response after simulated post-exposure vaccination?
1. Is there a difference in cellular and humoral immune responses induced by
the two immunization regimes?
2. Is there a difference in kinetics of the immune response during immunization?
3. Is adaptive and innate immune activation/ modulation during immunization
related to a differential degree of antigen exposure during immunization and
booster response after simulated PEP?
Is there a set of biomarkers on transcriptional level that predicts an adequate
anamnestic response?
Background summary
The main purpose of prophylactic rabies pre-exposure immunization (PrEP) is to
induce an effective and rapid anamnestic antibody response after revaccination
that obviates the need for human rabies immunoglobulins (RIG) and simplifies
post-exposure immunization (PEP) to just 2 doses of rabies vaccine (D0, D3) in
case of high risk bite wound.
Many travellers decline pre-travel 3-dose PrEP because of costs and
insufficient time between visit at the travel clinic and departure.
If a single dose of rabies vaccine would be equally effective in inducing a
rapid and adequate anamnestic antibody response, guidelines on pre-travel PrEP
could be simplified. Pre-travel rabies PrEP would come within reach of most
travellers.
Study objective
The aim of this study is to demonstrate that a single dose of rabies vaccine
can induce an equally rapid and adequate anamnestic antibody response as 2-dose
PrEP to revaccination six months later.
Study design
randomized controlled non-inferiority study
Intervention
Travellers will be randomized between standard 2-dose PrEP (D0, D7), single
dose PrEP (standard intramuscular dose or one-fifth fractional intradermal
dose) or no PrEP before travel. After 6 months, all subjects receive a
simulated 2-dose post-exposure vaccination schedule (D0 and D3). Serum samples
are collected at 0, 2, and 6 months after PrEP, and at 0, 3, 7 and 21 days
after the simulated post-exposure vaccinations
Study burden and risks
In total, 3 to 4 injections will be given with a registered rabies vaccine. A
maximum of 416 mL of blood will be collected during 8 sampling moments. Up to
eight visits are required for the study. Participants are asked to complete a
diary for safety evaluation during the study. Participants will be interviewed
on risk perception and health beliefs concerning bite wounds and rabies. In the
Netherlands intradermal administration of rabies vaccine is off-label use.
However, intradermal administration is safe and effective. The intradermal
route of administration is endorsed by the WHO for pre- and post-exposure
rabies vaccination. No risks are associated with participation in this study
other than those of routine vaccination and minimal to moderate physical
discomfort that can be experienced after vaccination or the collection of
blood. Participants will receive financial compensation for their
participation. Participants will have documented adequate levels of rabies
virus neutralizing antibodies (RVNA) after completing the study
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Travellers visiting the travel clinics of AMC, "Tropen Advies Centrum - Travel Clinic Harbour Hospital" and LUMC will be invited to participate in this study. In order to be eligible to participate in this study, a subject must meet all of the following criteria:
Age >=18 years
Travelling for less than 8 weeks
Expected time of departure >1 weeks
Good health according to investigator
Willingness and ability to adhere to the study regimen
Able to provide informed consent
Exclusion criteria
Previous vaccination against rabies vaccine
Requirement for standard rabies PrEP according to the national guidelines
Suspected previous vaccination against rabies
Known or suspected severe allergy against egg protein
Known or suspected allergy against any of the other vaccine components
History of unusual or severe reactions to any previous vaccination
History of (pre)syncope associated with medical procedures involving needles
Immunocompromized state due to illness or medication
Administration of plasma or blood products three months prior to inclusion
(hydroxy)chloroquine or mefloquine use
History of any neurological disorder including epilepsy
Pregnancy or breastfeeding
Any current infectious disease other than seasonal cold
Bleeding disorders or use of anticoagulants
Temporary exclusion criterion for vaccination: body temperature >= 38.5°C or acute illness will lead to postponement of participation and vaccination. Screening may continue when the temperature has normalized.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000089-31-NL |
| CCMO | NL60550.056.17 |
| OMON | NL-OMON24881 |