Immunogenicity and Safety PCV-20 of the Vaccine Administered During an Acute Febrile Illness in Adults

Patients at-risk of IPD are very frequently hospitalized for acute febrile illnesses. More than 50 % of the IPD at-risk patients hospitalized for an IPD or a pneumonia have been admitted to the hospital during the past 5 years without receiving a pneumococcal vaccination. Hospitalization appears to be therefore an opportunity to provide vaccines. However, physicians usually consider that vaccines should be postponed during an acute febrile illness including if non-severe. This consideration of not vaccinating during an acute febrile illness is however not evidence-based. This is associated to concerns about a potential risk of an impaired response to the vaccine and safety. In children, data about vaccination during a febrile illness have shown no safety nor efficacy concerns. In most countries, recommendations regarding this particular point are unclear.

In fine, vaccination is then rarely provided during the hospital stay as well as after discharge including in the USA, a country where it is recommended to vaccinate whatever the body temperature is and during hospitalization. Reluctance to immunize adults in this situation is probably due to the absence of evidence showing that it is as effective and safe as vaccinating patients without an acute or febrile illness.

To reduce the number of missed opportunities to immunize adults against S. pneumoniae, investigators aim to demonstrate that the administration of PCV-20 during an acute non-severe febrile illness is non-inferior than the administration one month after fever resolution in terms of immunogenicity (assessed by vaccine types (VT) Immunoglobulin G (IgG) concentrations and at least 2-fold change increase), and that it is as safe.

Inclusion criteria

• 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)
• Having at least one comorbidity that defines patients as medium or high risk for pneumococcal invasive infection:

• 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
• Social security affiliation
• Signed informed consent

Exclusion criteria

• 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
• Patient having received another vaccination within one month prior to inclusion or planning another vaccination in the month after inclusion except for Influenza vaccine.
• Patient with history of bone marrow transplantation
• Patient with haematological malignancies
• Patient under chemotherapy for solid tumor or with a history of chemotherapy in the past three months
• Patient treated with Rituximab currently or in the past 6 months
• Patient with Sequential Organ Failure Assessment (qSOFA ) score ≥ 2 at randomization (acute severe febrile illness)
• Patient hospitalized in an Intensive Care Unit
• Pregnancy
• Breastfeeding woman
• Recipients of polyclonal gammaglobulins in the past three months
• Inability to follow the protocol
• Bleeding disorder contra-indicating intramuscular injection according to the investigator
• History of allergy to PCV-20 or vaccine-related components.
• S. pneumoniae infection with laboratory confirmation (blood culture, culture from a sterile site, urinary or Cerebrospinal fluid antigens, sputum culture with > 10^7 colony forming unit (CFU)/mL) being the cause of the current hospitalization