Serological Response to Antipneumococcal Vaccination and Impact on Streptococcus Pneumoniae Nasal Carriage in HIV Adults (PCV13HIV2011)

Serological Response to Antipneumococcal Vaccination and Consequent Impact on Streptococcus Pneumoniae Nasal Carriage in HIV Positive Adults: a Prospective Study Using 13-valent Conjugate Vaccine

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Pneumococcal Infections
• Intervention / Treatment: Biological: pneumococcal conjugate 13 valent vaccine

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Istituto di Clinica delle Malattie Infettive, Policlinico Gemelli
  • Siena, Italy, 53100
    • UOC Malattie Infettive Universitarie, Policlinico Le Scotte

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 13-valent vaccine

Biological: pneumococcal conjugate 13 valent vaccine; Pneumococcal polysaccharide conjugate vaccine(13-valent adsorbed) conjugated to CRM197 carrier protein and adsorbed on aluminum phosphate (0.125 mg of aluminum). Pharmaceutical form: suspension for injection. Dosage: 0.5 ml, containing 2.2 g of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, and 4.4 micrograms for serotype 6B. Prevenar 13 is administered in two doses,each of 0.5 ml, with an interval of 2 months, injected intramuscularly in the deltoid muscle of the arm.; Other Names: Prevenar13

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Siena
• Collaborators: Ministry of Education, Universities and Research, Italy
• Investigators: Principal Investigator: Francesca Montagnani, MD, PhD, Universita di SIENA

Publications and helpful links

General Publications

• Belmonti S, Rossetti B, Modica S, Paglicci L, Borghetti A, Ciccullo A, Picarelli C, Cauda R, De Luca A, Montagnani F, Lombardi F. Long-Term Serological Response to 13-Valent Pneumococcal Conjugate Vaccine Versus 23-Valent Polysaccharide Vaccine in HIV-Infected Adults. Infect Dis Ther. 2019 Sep;8(3):453-462. doi: 10.1007/s40121-019-0256-z. Epub 2019 Jul 30.
• Lombardi F, Belmonti S, Fabbiani M, Morandi M, Rossetti B, Tordini G, Cauda R, De Luca A, Di Giambenedetto S, Montagnani F. Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study. PLoS One. 2016 Jun 3;11(6):e0156523. doi: 10.1371/journal.pone.0156523. eCollection 2016.
• Belmonti S, Lombardi F, Morandi M, Fabbiani M, Tordini G, Cauda R, De Luca A, Di Giambenedetto S, Montagnani F. Evaluation and Optimization of an ELISA Procedure to Quantify Antibodies Against Pneumococcal Polysaccharides Included in the 13-Valent Conjugate Vaccine. J Immunoassay Immunochem. 2016;37(2):189-200. doi: 10.1080/15321819.2015.1106949.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: December 13, 2013
• First Submitted That Met QC Criteria: April 23, 2014
• First Posted (Estimate): April 25, 2014

Study Record Updates

• Last Update Posted (Estimate): April 25, 2014
• Last Update Submitted That Met QC Criteria: April 23, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: HIV; Vaccine; Streptococcus pneumoniae; Immunological Response; 13-valent conjugate pneumococcal vaccine; Pneumococcal Carriage
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Infections; Communicable Diseases; Pneumococcal Infections; Pneumonia; Pneumonia, Pneumococcal; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 2011-004518-40 (EudraCT Number)