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

NCT ID: NCT02123433

Last Updated: 2014-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-10-31

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.

Conditions

HIV Infection; Pneumococcal Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

13-valent vaccine

Group Type: EXPERIMENTAL

pneumococcal conjugate 13 valent vaccine

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Prevenar13

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Education, Universities and Research, Italy

OTHER

Sponsor Role: collaborator

University of Siena

OTHER

Sponsor Role: lead

Responsible Party

Francesca Montagnani

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francesca Montagnani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Università di Siena

Locations

Istituto di Clinica delle Malattie Infettive, Policlinico Gemelli

Roma, , Italy

UOC Malattie Infettive Universitarie, Policlinico Le Scotte

Siena, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 31364010 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27258647 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26506438 (View on PubMed)

Other Identifiers

2011-004518-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2011-004518-40

Identifier Type: -

Identifier Source: org_study_id