Maternal Immunization With MenAfriVac™

• Signed/thumb-printed informed consent for trial participation obtained*
• Pregnant woman aged between 18 and 40 years of age inclusive* (note that those over 33 years of age would not be expected to have been vaccinated in the national MenAfriVac™ campaign targeting 1 to 29 years olds in Nov/Dec 2013)7
• Singleton pregnancy*
• From 28 to 34 weeks gestation as determined by ultrasound scan
• Resident within easy reach of the clinical trial site (no fixed boundaries will be set, and such judgements will be made on a case by case basis by members of the field team in discussion with the potential participant, taking into account knowledge of the local transport links and geography) *
• Intention to deliver at the health centre related to the clinical trial site (i.e. Faji Kunda health centres) *
• Willingness and capacity to comply with all the study procedures, including those relating to the newborn infant, in the opinion of the principal investigator or delegee

Exclusion Criteria:

• History of pre-eclampsia or eclampsia*
• History of gestational diabetes*
• Rhesus negative multigravida who did not receive anti-D in previous pregnancies
• Five or more previous pregnancies (grand-multigravida)
• Previous late stillbirth (defined as loss of pregnancy at any time after 28 weeks gestation) *

• Previous premature delivery (defined as delivery before 37 weeks gestation) *

  • Previous neonatal death (defined as death of an infant within the first 28 days of life) *
• Previous Caesarean section*
• Previous delivery of an infant with major congenital anomalies (see Table 7 for definition) *
• Previous delivery of an infant with a known or suspected genetic9 or chromosomal abnormality*
• History of other significant pregnancy related complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected*
• History of other significant neonatal complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected*
• Significant complications in current pregnancy
• Significant alcohol consumption during current pregnancy
• Significant maternal chronic illness including but not limited to hypertension requiring treatment, heart disease, lung disease, neurological disorders including a history of epilepsy or recurrent afebrile seizures, kidney disease, liver disease, anaemia and other haematological disorders, endocrine disorders including known diabetes mellitus, autoimmunity
• Severe anaemia (\<7.0g/dL) [35] *
• Known Human Immunodeficiency Virus (HIV) or hepatitis B (HBV virus positive or found to be HIV or HBV positive during screening*
• Positive result for syphilis infection on laboratory testing*
• Receipt of any vaccine during the current pregnancy or plans to receive any non-study vaccines during the current pregnancy (tetanus toxoid vaccination is not an exclusion and vaccines given during national campaigns if applicable will not generally be exclusions)
• Any other condition judged to significantly increase the risks to either the mother or the infant within the current pregnancy (including relevant history from previous pregnancies)
• History of anaphylactic or severe allergic reactions to previous vaccines or history of anaphylactic or severe allergic reactions in previous offspring (if applicable) *
• Receipt of any blood product including human immunoglobulins at any stage during the current pregnancy or plan to receive any blood products during the period of trial participation (receipt or blood products in an emergency or for obstetric reasons will not represent a protocol deviation given such situations are unplanned)
• Receipt of immunosuppressive or immuno-modulatory medication at any stage during the current pregnancy or plan to receive any such medication during the period or trial participation
• Clinically suspected or confirmed congenital or acquired clotting or bleeding disorders or the current receipt of medications known to alter clotting or bleeding*
• Current malaria infection (on the day of vaccination)
• Any clinically significant signs or symptoms of acute illness, significant abnormalities in vital signs, an axillary temperature of > 37.5°C or any recorded fever (> 37.5°C) in the preceding 24 hours.
• 2 or more symptoms (nausea/vomiting, diarrhoea, headaches, fatigue and myalgia) rated as grade 2 and clinically significant on the maternal systemic reactogenicity scale (Table 5) present at baseline on the day of vaccination

In cases on uncertainly, the clinical significance of any particular complaint will be judged by the PI, in discussion with other members of the clinical trial team. The safety of the expectant mother and unborn infant will always represent the key criteria with this regard. The basis of such decisions will be documented in the participant notes maintained by the clinical trial team.

In the case of an acute illness, including malaria, documented fever or abnormalities in vital signs, and also when 2 or more grade 2 systemic reactogenicity symptoms are present, the potential participant will not be deemed to be a screen failure and thus will not be permanently excluded from participation (unless the assessing clinician has reason be believe the problem will persist). Under these circumstances the expectant mother will be termed a temporary exclusion and will be re-screened at an appropriate interval for eligibility (a minimum of 24 hours in the case of a recorded fever and otherwise according to the clinical judgement of the clinician). If 34 weeks gestation passes during this period of observation, if any other inclusion criteria is no longer met (e.g. the potential participant reaches her 41st birthday) or if another exclusion criteria is met (e.g. the potential subject develops pre-eclampsia), the participant will be deemed to be a screen failure. Repeat serological testing for HIV, Hepatitis B and syphilis is not required at re-screening unless the PI has specific reason to believe that a potential participant's status may have changed in the interval since the original test. A repeat haemoglobin level is not required although may be undertaken if judged to be warranted on the basis of clinical assessment.