Safety and Immunogenicity Following Meningococcal and Pneumococcal Immunization Among Adult People Living With HIV

Study Overview
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Brief Summary
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MENPI is an investigator-initiated single-centre randomized controlled trial which aims to assess the efficacy and safety of meningococcal and pneumococcal vaccination in adults living with HIV receiving antiretroviral treatment. Participants are randomized 1:1 to either a two-dose Menveo® and Bexsero® regimen or a Prevenar13®/Pneumovax23® prime-boost regimen at day 0 and day 60 and cross over on day 90. All participants will follow an identical follow up program including plasma collection, pharyngeal swab, and adverse event registration. Immunogenicity will be determined on venous blood sampled at 30 days post-vaccination and yearly for five years.

Official Title
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Safety and Immunogenicity Following Meningococcal and Pneumococcal Immunization Among Adult People Living With HIV: A Single Center, Non-blinded, Randomized Clinical Trial

Conditions
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Hiv, Meningococcal Infections, Pneumococcal Infections

Intervention / Treatment
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* Drug: Neisseria meningitidis oligosaccharide conjugate vaccine and recombinant protein-based vaccine
* Drug: 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Seropositive for HIV-1 Recipient of ART Plasma HIV-RNA < 500 copies/ml Patients written consent obtained Exclusion Criteria: Pregnancy or breastfeeding History of meningococcal or pneumococcal vaccination Allergies towards any of the vaccine components Temperature > 38 ᵒC Sign of bacterial infection Previous known or suspected disease caused by N. meningitidis Active AIDS associated illness Active malignancy End-stage renal or liver disease Bleeding disorder Recipient of any blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within the last month Use of immunosuppressive agents (corticosteroids, cancer chemotherapeutic agents etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menveo + Bexsero<br> | Drug: Neisseria meningitidis oligosaccharide conjugate vaccine and recombinant protein-based vaccine<br>* One dose (0.5 ml) of conjugate vaccine against meningococcal serogroups ACWY (Menveo®) and one dose of a recombinant protein-based vaccine against meningococcal serogroup B (Bexsero®) at day 0 followed by another dose (0.5 ml) of each vaccine at day 60.<br>* Other names: Menveo® and Bexsero®;|
| Experimental: Prevenar13 + Pneumovax23<br> | Drug: 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine<br>* One dose (0.5 ml) of pneumococcal conjugate vaccine (Prevenar13®) at day 0 and one dose (0.5 ml) of pneumococcal polysaccharide vaccine (Pneumovax23®) at day 60.<br>* Other names: Prevenar13® and Pneumovax23®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in immunogenic response from baseline, Menveo | A ≥4-fold rise in rabbit complement source (rSBA) for the four serogroups A, C, Y, and W-135. Seroprotection is defined as an rSBA titre ≥1:8 and patients will be classified as previously immune if baseline rSBA is ≥1:8. | Day 30 and year 1, 2, 3, 4, and 5 post-vaccination | 
| Change in immunogenic response from baseline, Bexsero | A ≥4-fold rise in antibody titers against a panel of four meningococcal serogroup B reference strains between pre-vaccination and post-vaccination timepoints, or a post-vaccination antibody titre ratio of ≥1:4 for individuals who were seronegative before vaccination. | Day 30 and year 1, 2, 3, 4, and 5 post-vaccination | 
| Change in immunogenic response from baseline, Prevenar13/Pneumovax23 | A ≥2-fold rise in serum anti-capsular IgG GMC for 12 shared pneumococcal polysaccharides (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) | Day 30 and year 1, 2, 3, 4, and 5 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate adverse events |  | 30 minutes post-vaccination | 
| Number of participants with short term adverse events |  | Day 5 post vaccination | 
| Number of participants with long term adverse events |  | Day 90 post-vaccination | 
| Streptococcus pneumoniae carriage rates | Proportion of study subject with a culture or PCR positive pharyngeal swab sample | Baseline and day 30 post-vaccination | 
| Neisseria meningitidis carriage rates | Proportion of study subject with a culture or PCR positive pharyngeal swab sample | Baseline and day 30 post-vaccination |