A Phase IV Study to Evaluate the Immunogenicity and Safety in UK Laboratory Workers of Menitorix
A Phase IV Study to Evaluate the Immunogenicity and Safety in UK Laboratory Workers of Menitorix
Menitorix is a combined Hib conjugate and meningococcal C conjugate vaccine made by
 GlaxoSmithKline. It is currently licensed and recommended as a booster vaccination for UK
 children in the second year of life.

 It is important that staff who have a potential occupational exposure to infectious disease
 are afforded protection where possible. The licensure and availability of Menitorix provides
 the opportunity to vaccinate such staff.

 Immune responses that are indicative of protection have been established for both Hib and
 meningococcal C disease. It is therefore proposed that the immune responses of those
 laboratory staff taking part be measured as data currently available following Menitorix
 vaccination is in naïve children and adults. This study will also allow us to provide
 occupational healthcare to laboratory workers.

 Participation in the study would be offered to all those staff considered to be at
 occupational health risk of Hib or meningococcal C disease at the Manchester HPA site. This
 will be a single group study in that everyone enrolled will receive a single dose of
 Menitorix and will have blood collected prior to and 4-6 weeks following vaccination.

 Assessment of whether protective levels of antibody have been achieved will be made using the
 blood sample taken 4-6 weeks after vaccination. Extra dose(s) will be offered to any subjects
 whose levels are not considered to confer protection as described later in this protocol.
 Subjects receiving and extra vaccination will be offered and a further blood test 4-6 weeks
 later to allow antibody levels to be checked again.
Menitorix is a combined Hib conjugate and meningococcal C conjugate vaccine made by
 GlaxoSmithKline. It is currently licensed and recommended as a booster vaccination for UK
 children in the second year of life.

 It is important that staff who have a potential occupational exposure to infectious disease
 are afforded protection where possible [HPA Occupational Health Policy [Appendix 1]; HSE Safe
 working and the prevention of infection in clinical laboratories and similar facilities,
 2003]. The licensure and availability of Menitorix provides the opportunity to vaccinate such
 staff.

 Immune responses that are indicative of protection have been established for both Hib and
 meningococcal C disease [Andrews et al., 2003; Kayhty et al., 1983]. It is therefore proposed
 that the immune responses of those laboratory staff taking part be measured as data currently
 available following Menitorix vaccination is in naïve children and adults [Tejedor et al.,
 2006a and b; Carmona et al., 2006; Habermehl et al., 2006; Pace et al., 2006]. This study
 will also allow us to provide occupational healthcare to laboratory workers.

 Laboratory staff at Manchester have not received a Hib vaccine although they have received a
 number of meningococcal vaccines with the majority having received their meningococcal
 serogroup C conjugate vaccine in 1999. Certain staff would have received bivalent
 meningococcal A and C prior to the conjugate vaccine which has recently been demonstrated to
 hinder the induction of immunological memory by the conjugate vaccine [Vu et al., 2006].
 Following the conjugate vaccine many staff have since received a quadrivalent A/C/Y/W135
 polysaccharide vaccine in the following seven years, but little is known about the duration
 of protection in this age group.

 Receiving a polysaccharide vaccine following a conjugate does induce an elevated antibody
 response but it is known that polysaccharide vaccination does not generate memory B cells and
 can result in the loss of the ability to mount subsequent memory antibody responses, as was
 observed by MacLennan et al. for Neisseria meningitidis group C anticapsular antibody
 responses [MacLennan et al., 2001]. The clinical importance of loss of immunological memory
 or induction of antibody hyporesponsiveness, is unknown. However, in addition to dampening
 antibody responses to a subsequent immunisation, a delay or impaired serum antibody response
 upon encountering an encapsulated pathogen could theoretically increase susceptibility to
 developing disease. Such a mechanism may explain the higher rate of otitis media observed
 after administration of 23-valent pneumococcal polysaccharide vaccine to Dutch children
 primed with a 7-valent pneumococcal polysaccharide protein conjugate vaccine as compared with
 the rate in controls given hepatitis B vaccine (P=0.0001) [Veenhoven et al., 2003]. In
 contrast, during the six months between the conjugate vaccination and booster there was a
 trend in favor of fewer episodes of otitis in the pneumococcal-vaccinated group.

 It appears that staff will benefit from both the Hib and serogroup C conjugate vaccinations.

 Assessments in this study:

 Participation in the study would be offered to all those staff considered to be at
 occupational health risk of Hib or meningococcal C disease at the Manchester HPA site. The
 maximum number of participants would therefore be 30. This will be a single group study in
 that everyone enrolled will receive a single dose of Menitorix and will have blood collected
 prior to and 4-6 weeks following vaccination.

 Local anaesthetic cream will be offered to minimise discomfort of the blood tests and fully
 trained staff will carry out all procedures.

 Assessment of whether protective levels of antibody have been achieved will be made using the
 blood sample taken 4-6 weeks after vaccination. Extra dose(s) will be offered to any subjects
 whose levels are not considered to confer protection as described later in this protocol.
 Subjects receiving and extra vaccination will be offered and a further blood test 4-6 weeks
 later to allow antibody levels to be checked again.

 Samples will be sent to collaborating laboratories of the National Vaccine Evaluation
 Consortium for assessment of responses to vaccinations.
Inclusion Criteria:

 -  No contraindications to vaccination as specified in the "Green Book" - Immunisation
 Against Infectious Disease, HMSO.

 -  Written informed consent

 Exclusion Criteria:

 -  Known or suspected pregnancy