Streptococcus pneumoniae is responsible for serious infections associated to numerous hospitalizations and high rate of mortality. The incidence and therefore the burden of pneumococcal infections have been significantly reduced thanks to the use of pneumococcal conjugate vaccines (PCVs). PCVs were shown to be effective against vaccine-type serotypes causing both non-invasive and invasive pneumococcal diseases (IPD) in children and adults. PCVs use in children was shown to have an impact on IPD incidence among adults due to herd immunity and on antimicrobial resistance. To increase the protection of at-risk patients against IPD, the 20-valent PCV (PCV-20) is recently recommended in adults, after a period where PCV-13 followed by pneumococcal polysaccharide vaccine 23 valent (PPV-23) was recommended. PCV-20 effectiveness against IPD and against pneumonia was inferred from immunobridging with PCV-13. Indeed PCV-13 was shown effective to reduce the incidence of low respiratory tract infections and IPD (bacteraemia and meningitis) in 65-years-old-adults and older. Currently immunization against S. pneumoniae is recommended with PCV-20 for adult patients at-risk for IPD such as immunocompromised (=high-risk patients) and in immunocompetent people with underlying chronic conditions (cardiovascular, liver, pulmonary, kidney diseases and diabetes mellitus) (=medium risk patients). However, vaccine coverage against IPD in adults remains low globally, and does not exceed 5 % in France. Reducing missed opportunities of vaccination for S. pneumoniae is crucial.
History of body temperature ≥ 38°C measured at least twice prior to randomization (Randomization must be performed as soon as possible on a febrile patient or 72 hours after apyrexia at the latest)
Medium risk: Cyanogenic congenital heart disease; chronic heart failure; chronic respiratory failure; chronic obstructive pulmonary disease; emphysema; severe asthma under chronic treatment; chronic renal failure; chronic liver disease; diabetes mellitus treated; Osteo-meningeal leak or cochlear implant; Age > 65 years old.
High risk : Hypo or asplenic people; hereditary immunodeficiency syndromes; people living with HIV; solid organ transplanted; People under immunosuppressors (corticosteroids, biotherapy) for an auto-immune or an inflammatory chronic disease; patients with nephrotic syndrome
Hospitalization for > 24 hours long
Patient unable to give informed consent
Curators, wardship
History of previous vaccination with PCV-7 or PCV-13 or PCV-20
History of PPV-23 in the previous year
Parallel
Early intervention
Biological/VaccineIn this arm, patient will receive unique dose of the PCV-20 vaccine (Prevnar 20) as soon as possible and until 72h after apyrexia. The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.
Delayed intervention
Biological/VaccineIn this arm, from 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature \< 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive unique dose of the PCV-20 vaccine (Prevnar 20). The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.
Proportion of immune "good responders" to PCV-20 in both arms
Good responders is defined as - a seroconversion (a 2-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG \> 1,3 μg/mL in ≥ 10 out 13 VT. OR \- -a seroconversion (a 4-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG \< 1,3 μg/mL in ≥ 10 out 13 VT.
Safety endpoints in both arms in the month following vaccination : adverse events
Number, type and severity of solicited (in the 7 days following vaccination) and unsolicited (in the month following vaccination) adverse events
Frequency of local reactions
Local reactions will be defined as : pain, redness, and swelling at the study vaccine injection site and limitation of arm movement
Frequency of systemic events related to the vaccination
Onset or worsening of fever, diarrhoea, chills, fatigue, headache, vomiting, decreased appetite, rash, muscle pain, joint pain). An independent blinded central adjudication committee will define the onset or worsening of symptoms and will review all systemic events.
Proportion of immune good responders serotype by serotype
"Good responders" being defined above (primary end-point) A blood sample for immunologic analysis will be performed
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Centre Hospitalier Universitaire de Saint Etienne
Lead sponsor
Ministry of Health, France
Collaborator
IREIVAC/COVIREIVAC Network
Collaborator
