Clinical Trials

MainTitle

Antibodies and Memory Cells Role After Different Pneumococcal Vaccines in HIV Adults

This study has been withdrawn
Sponsor
University of Siena

Collaborator
Catholic University of the Sacred Heart

Information provided by (Responsible Party)
Francesca Montagnani, University of Siena

ClinicalTrials.gov Identifier
NCT02357823

First received: January 22, 2015
Last updated: January 9, 2017
Last Verified: January 2017
History of Changes
Purpose

Purpose

Streptococcus pneumoniae is a cause of high morbidity and mortality in HIV-positive subjects, representing the leading etiological agent of severe bacterial pneumonia. International guidelines recommend that HIV positive patients aged >=19 years, who are 13-valent conjugate vaccine (PCV13) naïve, should receive a single dose of PCV13. Pneumococcal polysaccharide vaccine 23-valent (PPV23) should be given >=8 weeks after indicated dose of PCV13, and a second dose of PPV23 should be given 5 years later. For those who previously received PPV23, PCV13 should be administered >=1 year after the last PPV23 dose. HIV infection affects humoral immunity both through reduced T-cell help and changes in the B-cell compartment. Neither amount of circulating memory B cells nor their functions are restored by antiretroviral therapy: this may affect antibody mediated immunity, even in well-treated HIV patients. In asplenic childrens a single dose of PCV13 seems sufficient to restore the pool of anti-pneumococcal polysaccharides IgG memory B cells. In adults, it has been reported that a single dose of 7-valent pneumococcal conjugate vaccine induces significant increases in serotype-specific memory B-cell populations, conversely, immunization with PPV23 seems to decrease memory B-cell frequency. However, data on immunological response after PCV13 in HIV positive adults are still scanty and the optimal pneumococcal prophylaxis strategy needs further investigation. Number of PCV13 doses is actually demanded to clinical judgment for each patient; also current Italian indications recommend at least one dose, but till 3 doses seem to be suggested for immunocompromised patients. Present study aims to investigate short and long term immunological response after different standard vaccine schedule and to evaluate pneumococcal nasopharyngeal colonization in vaccinated patients.

Condition Intervention
HIV
Pneumococcal Infections

Other : Evaluation of immunological response
Other : Nasopharyngeal swabs analysis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Long Term Serological Response and Memory Cells Role After Different Pneumococcal Vaccine Strategies in HIV Adults

Further study details as provided by Francesca Montagnani, University of Siena:

Primary Outcome Measures

  • Immunological response evaluation [ Time Frame: 24 months ]
    Dosing of serotype specific antibodies (cut off value: 0.35 mcg/mL for each vaccine polysaccharide antigen) and quantification of number and phenotype of serotype specific B cells
Secondary Outcome Measures:
  • Streptococcus pneumoniae colonization [ Time Frame: 24 months ]
    Presence of S. pneumoniae in nasopharyngeal swabs culture

Biospecimen Retention: Samples Without DNA
Microbes isolated from nasopharingeal swab; blood for analysis of immune response

Enrollment: 0
Study Start Date: January 2015
Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Group 1
Immunological and microbiological status of HIV- positive adults with pneumococcal vaccinal status of 2 PCV13 doses received from more than 3 years that have prescription for a single booster dose of PCV13.
Other: Evaluation of immunological response

Study of short and long term immunological response after different schedule of PCV13 or PPV23

Other: Nasopharyngeal swabs analysis

Evaluation of pneumococcal nasopharyngeal colonization

Group 2
Immunological and microbiological status of HIV- positive adults with pneumococcal vaccinal status of 1 PPV23 dose received from more than 3 years that have prescription to receive 2 doses (priming + boost) of PCV13.
Other: Evaluation of immunological response

Study of short and long term immunological response after different schedule of PCV13 or PPV23

Other: Nasopharyngeal swabs analysis

Evaluation of pneumococcal nasopharyngeal colonization

Group 3
HIV- positive adults that have never received a pneumococcal vaccine (naive) and have a CD4+ cell count < 200 cells/ul that have prescription to be primed with a single dose of PCV13 then boosted with a single dose of PPV23.
Other: Evaluation of immunological response

Study of short and long term immunological response after different schedule of PCV13 or PPV23

Other: Nasopharyngeal swabs analysis

Evaluation of pneumococcal nasopharyngeal colonization

Group 4
Immunological and microbiological status of HIV- positive adults that have never received a pneumococcal vaccine (naive) and have a CD4+ cell count > 200 cells/ul that have prescription to be primed with a single dose of PCV13 then boosted with a single dose of PPV23.
Other: Evaluation of immunological response

Study of short and long term immunological response after different schedule of PCV13 or PPV23

Other: Nasopharyngeal swabs analysis

Evaluation of pneumococcal nasopharyngeal colonization

Group 5
Immunological and microbiological status of HIV- positive adults with pneumococcal vaccinal status of 1 PPV23 dose received from more than 3 years and that that have prescription to receive a single dose of PCV13.
Other: Evaluation of immunological response

Study of short and long term immunological response after different schedule of PCV13 or PPV23

Other: Nasopharyngeal swabs analysis

Evaluation of pneumococcal nasopharyngeal colonization

Detailed Description:

The study will be divided in 3 main aims; in the first, the long term immunological response to PCV13 and PPV23 in HIV+ adults will be evaluated. In a previous clinical trial (PRIN 2009 study, Clinicaltrials: NCT02123433) a cohort of HIV positive adults had been vaccinated either with 2 doses of PCV13 8 weeks apart or 1 dose of PPV23 (last enrollment: December 2012). Immunoglobulins G (IgGs) against 12 common pneumococcal serotypes included in PCV13 and PPV23 were quantified by ELISA at baseline (BL), 8, 24 and 48 weeks: analysis are still ongoing; preliminary data revealed that both vaccines were safe and well tolerated and showed similar immunogenicity. The present study aims to evaluate persistence of long term (>= 3 years) serological and memory B cells response in those previous vaccinated groups. In this phase, population will be screened for inclusion and exclusion criteria to entire study conduction. Once obtained informed consent, patients will be enrolled. Together with the collection of blood samples for routine purposes, an additional blood sample will be taken so to run immunological tests (ELISA, ELISpot). It is important to underline that no invasive procedures are needed for the study, apart from routine clinical practice: blood specimens will be obtained as part of routine investigations, blood will be hence taken for CD4+ cell count, viraemia analysis and anti-HIV drug monitoring; enrolled patients will agree just to donate a blood sample for research purposes. Blood samples will be collected from all previously PCV13 or PPV23 vaccinated HIV+ subjects and serum antibodies and B cells isotypes will be analyzed at baseline (BL), that is >= 3 years after a previous PCV13 or PPV23 vaccination.
The second objective of this study aims to evaluate short and long term immunological response with different combined vaccine strategies in HIV+ adults. Participants will be recruited if they'll have needed to receive antipneumococcal vaccines (primary or booster) according to clinical standard indications.
Elicited immunological response (serum antibodies and B cells isotypes) will be explored at BL, 8, 24, 48 and 96 weeks after additional different received pneumococcal vaccine strategies. At BL, after collecting blood samples as previously described for Aim1, every patient will be assigned to a specific Group on the basis of the received vaccine schedule, prescribed by clinicians according to individual clinical indications. Short- (30 minutes), medium- (<=5 days) and long-term adverse reactions will be reported, by clinical evaluation within 30 minute post-vaccine, phone call at day 5 and anamnestic data collection during follow up 8, 24, 48 and 96 weeks.
Blood samples will be analyzed at 8, 24, 48 and 96 weeks to evaluate serum antibodies and B cells isotypes.
Finally, the third aim of the study will lead an epidemiological and microbiological survey in vaccinated HIV+ adults. At BL, 8, 24, 48 and 96 weeks all clinical-anamnestic data will be updated, together with blood sample analysis to title IgG towards each vaccinal pneumococcal polysaccharides and to evaluate B cells isotypes and nasopharyngeal swab for S. pneumoniae culture, in vitro chemosusceptibility tests, serotyping, clonal analysis by Multilocus Locus Sequence Typing (MLST).
Carriage will be defined as S. pneumoniae isolation from one or more of the nasal swabs, in absence of any clinical signs or symptoms; a 12 months clinical follow up will be performed in colonized patients. All patients developing infections will be followed until resolution.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  
Sampling Method: Non-Probability Sample  

Study Population

HIV-positive adults that undergo the International and Italian Ministry of Health indications for administration of pneumococcal vaccines.

Criteria

Inclusion Criteria:

  • age between 18 and 65 years
  • acceptance of informed consensus
  • HIV positivity
  • access to structures in ambulatory or Day Hospital regimen
  • CD4+ cell count > or < than 200 cells/ul
  • subjects for which Italian Ministry of Health recommend pneumococcal vaccination with PCV13 or PPV23


Exclusion Criteria:
  • pregnancy
  • acute infectious disease ongoing
  • antibiotic therapy ongoing in the previous 7 days
  • HIV-independent immunodepression
  • chronic steroid therapy
  • anatomic or functional asplenia
  • contraindication to vaccination based on package insert drug facts, such as
hypersensitivity to the active ingredient or one of the bulking agents (PPV23, Pneumovax);hypersensitivity to the active ingredient, to one of the bulking agents or to the diphteria toxoid (PCV13, Prevenar 13)

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02357823

Locations

Italy
Istituto di Clinica delle Malattie Infettive c/o Policlinico Gemelli, Largo Agostino Gemelli 12
Roma, Rome, Italy, 00168
UOC Malattie Infettive Universitarie c/o Policlinico Le Scotte, Viale Mario Bracci 16
Siena, Italy, 53100

Sponsors and Collaborators

University of Siena
Catholic University of the Sacred Heart

Investigators

Principal Investigator: Francesca Montagnani, MD, PhD Università degli Studi di Siena - Dipartimento di Biotecnologie Mediche - Dipartimento di Malattie Infettive Universitarie
More Information

More Information


Responsible Party: Francesca Montagnani, Md, PhD, University of Siena  
ClinicalTrials.gov Identifier: NCT02357823   History of Changes  
Other Study ID Numbers: PCV13HIV-BOOST-2013  
Study First Received: January 22, 2015  
Last Updated: January 9, 2017  

Keywords provided by Francesca Montagnani, University of Siena:

Pneumococcal vaccine
HIV infection
13-valent Pneumococcal Conjugate Vaccine
23-valent Pneumococcal Polysaccharide Vaccine

Additional relevant MeSH terms:
Pneumococcal Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine

ClinicalTrials.gov processed this data on December 08, 2017
This information is provided by ClinicalTrials.gov.