Serological Response to Antipneumococcal Vaccination and Impact on Streptococcus Pneumoniae Nasal Carriage in HIV Adults

Phase 3

Completed

• Conditions: Pneumococcal Infections; HIV Infection
• Interventions: Biological: pneumococcal conjugate 13 valent vaccine

• Registration Number: NCT02123433
• Lead Sponsor: University of Siena

Brief Summary

S. pneumoniae is frequently isolated from nasal swabs of healthy subjects, but it can also cause severe diseases (pneumonia, bacteraemia, meningitis and sepsis).HIV-infected subjects are more sensitive to invasive diseases and recurrent infection than the general population. Nasal carriage is the main pathogenetic feature for invasive disease: bacteraemia is more frequent in carriers, HIV+ patients are constantly colonized by the same pneumococcal strain and their nasopharyngeal isolates have features similar to subsequent invasive strains. A 23-valent polysaccharide vaccine (PPV23) has long been available and recommended in the HIV+ population as prophylaxis for invasive disease. Studies regarding efficacy of PPV23 in HIV+ are controversial and highlight that immune response induced by PPV23 in HIV+ is poor and an hyporesponsiveness to repeated polysaccaridic antigens stimulation can occur. Moreover, PPV23 seems not to affect pneumococcal carriage status and could lead to emergence of non-vaccine serotypes. The conjugation of pneumococcal capsular polysaccharides to carrier proteins results in an improved T-cell dependent immune response, characterized by increased antibody concentrations and induction of T and B memory cells, with a demonstrated higher efficacy in children. A heptavalent vaccine conjugated with diphtheria toxoid (PCV7) is approved in Europe since 2001 and is effective in reducing incidence of invasive disease by vaccine serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), in both children and adults, due to effect of herd immunity. A PCV13 formulation has recently been developed, covering PCV7 serotypes plus 1, 3, 5, 6A, 7F and 19A. PCV13 revealed the same safety profile as PCV7 in pediatric patients, that are the main target of conjugate vaccines licensure. Some trials showed a better antibody response in terms of quantity and quality in HIV + adults by using PCV7 as compared to PPV23. However these data were not unequivocally confirmed in further studies on the use of PCV7 alone or in combination with PPV23. The first trials of PCV13 use in adults showed the same or even better response compared to PPV23, with a safety and tolerability similar to PCV7. PCV13 in HIV+ adults is a promising candidate prophylactic measure for pneumococcal infections. The purpose of this study is to evaluate serological response and prevalence of nasopharyngeal colonization by S. pneumoniae in HIV+ non-hospitalized adults, following vaccination with 2 doses of PCV13.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Study First Submitted: 2013-12-13
• Status Verified: 2014-04
• Study First Submitted QC: 2014-04-23
• Last Update Submitted: 2014-04-23
• Study First Posted: 2014-04-25
• Last Update Posted: 2014-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• > 18 years old
• obtained informed consent
• outpatient
• CD4 ≥200 cells/µl in the last two evaluations before T0

Exclusion Criteria

• > 65 years old
• presence of acute infectious disease
• antibiotic therapy (ongoing or in the previous <= 7 days)
• previous PPV23 or PCV7 vaccination
• Pregnancy
• Current immunomodulatory therapy
• Immunosuppression not HIV related

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
13-valent vaccine	pneumococcal conjugate 13 valent vaccine	-

Primary Outcome Measures

Name	Time	Method
Serological response after 2 doses of PCV13 vaccine.	Twenty months	Measure of serological response after 2 doses of PCV13 vaccine (booster dose after 8 weeks) in HIV+ adults.
Pneumococcal nasopharyngeal colonization	Twenty months	to determine the rate of nasopharyngeal colonization by different pneumococcal serotypes in HIV-positive adults, in relation to baseline antibody titers at T0

Secondary Outcome Measures

Name	Time	Method
Pneumococcal chemosusceptibility	Twenty months	Number and percentages of antibiotic resistant (including multiresistant) strains
Molecular epidemiology	Twenty months	Molecular typing combining PFGE (Pulsed Field Gel Electrophoresis), MLST (MultiLocus Sequence Typing) and PCR analysis of bacterial isolates.

Trial Locations

Locations (2)

UOC Malattie Infettive Universitarie, Policlinico Le Scotte; 🇮🇹 Siena, Italy

Istituto di Clinica delle Malattie Infettive, Policlinico Gemelli; 🇮🇹 Roma, Italy