Phase I Clinical Evaluation of a Synthetic Oligosaccharide-protein Conjugate Vaccine Against Haemophilus Influenzae Type B in Human Adult Volunteers

Overview

Journal Clin Vaccine Immunol

Publisher American Society for Microbiology

Specialties Allergy & Immunology
Pathology

Date 2006 Sep 9

PMID 16960118

Citations 14

Authors

Gilda Torano

Maria E Toledo

Alberto Baly

Violeta Fernandez-Santana

Francisco Rodriguez

Yunia Alvarez

Teresita Serrano

Alexis Musachio

Ibis Hernandez

Eugenio Hardy

Arlene Rodriguez

Hector Hernandez

Aristides Aguilar

Raydel Sanchez

Manuel Diaz

Verena Muzio

Jorgelina Dfana

Maria C Rodriguez

Lazaro Heynngnezz

Vicente Verez-Bencomo

Affiliations

Soon will be listed here.

Abstract

Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.

Citing Articles

Analysis of immunogenicity and purification methods in conjugated polysaccharide vaccines: a new approach in fighting pathogenic bacteria.

Sheikhi A, Shirmohammadpour M, Mahdei Nasirmahalleh N, Mirzaei B Front Immunol. 2024; 15:1483740.

PMID: 39635523 PMC: 11614811. DOI: 10.3389/fimmu.2024.1483740.

Semisynthetic Glycoconjugate Vaccine Candidates against O25B Induce Functional IgG Antibodies in Mice.

Naini A, Bartetzko M, Sanapala S, Broecker F, Wirtz V, Lisboa M JACS Au. 2022; 2(9):2135-2151.

PMID: 36186572 PMC: 9516715. DOI: 10.1021/jacsau.2c00401.

Synthetic Pseudaminic-Acid-Based Antibacterial Vaccine Confers Effective Protection against Infection.

Wei R, Yang X, Liu H, Wei T, Chen S, Li X ACS Cent Sci. 2021; 7(9):1535-1542.

PMID: 34584955 PMC: 8461771. DOI: 10.1021/acscentsci.1c00656.

Recent advances on smart glycoconjugate vaccines in infections and cancer.

Anderluh M, Berti F, Bzducha-Wrobel A, Chiodo F, Colombo C, Compostella F FEBS J. 2021; 289(14):4251-4303.

PMID: 33934527 PMC: 9542079. DOI: 10.1111/febs.15909.

type b invasive infections in children hospitalized between 2000 and 2017 in a Pediatric Reference Hospital (PRH).

Delfino Sosa M, Zabala C, Pardo L, Fernandez L, Nieves C, Mas M Heliyon. 2020; 6(3):e03483.

PMID: 32215324 PMC: 7083785. DOI: 10.1016/j.heliyon.2020.e03483.

References

Griswold W, Lucas A, Bastian J, Garcia G . Functional affinity of antibody to the Haemophilus influenzae type b polysaccharide. J Infect Dis. 1989; 159(6):1083-7. DOI: 10.1093/infdis/159.6.1083. View

Kayhty H, Peltola H, Eskola J . Immunogenicity and reactogenicity of four Haemophilus influenzae type b capsular polysaccharide vaccines in Finnish 24-month-old children. Pediatr Infect Dis J. 1988; 7(8):574-7. View

Phipps D, West J, Eby R, Koster M, Madore D, Quataert S . An ELISA employing a Haemophilus influenzae type b oligosaccharide-human serum albumin conjugate correlates with the radioantigen binding assay. J Immunol Methods. 1990; 135(1-2):121-8. DOI: 10.1016/0022-1759(90)90264-v. View

Kayhty H, Eskola J, Peltola H, Ronnberg P, Kela E, Karanko V . Antibody responses to four Haemophilus influenzae type b conjugate vaccines. Am J Dis Child. 1991; 145(2):223-7. DOI: 10.1001/archpedi.1991.02160020117030. View

Peeters C, Evenberg D, Hoogerhout P, Kayhty H, Saarinen L, van Boeckel C . Synthetic trimer and tetramer of 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate conjugated to protein induce antibody responses to Haemophilus influenzae type b capsular polysaccharide in mice and monkeys. Infect Immun. 1992; 60(5):1826-33. PMC: 257080. DOI: 10.1128/iai.60.5.1826-1833.1992. View

Peltola H, Kilpi T, Anttila M . Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines. Lancet. 1992; 340(8819):592-4. DOI: 10.1016/0140-6736(92)92117-x. View

Slack M . Invasive Haemophilus influenzae disease: the impact of Hib immunisation. J Med Microbiol. 1995; 42(2):75-7. DOI: 10.1099/00222615-42-2-75. View

Steinhoff M . Haemophilus influenzae type b infections are preventable everywhere. Lancet. 1997; 349(9060):1186-7. DOI: 10.1016/S0140-6736(97)22017-9. View

Chong P, Chan N, Kandil A, Tripet B, James O, Yang Y . A strategy for rational design of fully synthetic glycopeptide conjugate vaccines. Infect Immun. 1997; 65(12):4918-25. PMC: 175709. DOI: 10.1128/iai.65.12.4918-4925.1997. View

10.

Fernandez-Santana V, Cardoso F, Rodriguez A, Carmenate T, Pena L, Valdes Y . Antigenicity and immunogenicity of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b. Infect Immun. 2004; 72(12):7115-23. PMC: 529110. DOI: 10.1128/IAI.72.12.7115-7123.2004. View

11.

Adams W, Deaver K, Cochi S, Plikaytis B, Zell E, Broome C . Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA. 1993; 269(2):221-6. View

12.

Peltola H . Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev. 2001; 13(2):302-17. PMC: 100154. DOI: 10.1128/CMR.13.2.302. View

13.

Romero-Steiner S, Fernandez J, Biltoft C, Wohl M, Sanchez J, Feris J . Functional antibody activity elicited by fractional doses of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate). Clin Diagn Lab Immunol. 2001; 8(6):1115-9. PMC: 96235. DOI: 10.1128/CDLI.8.6.1115-1119.2001. View

14.

Verez-Bencomo V, Fernandez-Santana V, Hardy E, Toledo M, Rodriguez M, Heynngnezz L . A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science. 2004; 305(5683):522-5. DOI: 10.1126/science.1095209. View

15.

Schneerson R, Rodrigues L, Parke Jr J, Robbins J . Immunity to disease caused by Hemophilus influenzae type b. II. Specificity and some biologic characteristics of "natural," infection-acquired, and immunization-induced antibodies to the capsular polysaccharide of Hemophilus influenzae type b. J Immunol. 1971; 107(4):1081-9. View

16.

Hornick C, Karuch F . Antibody affinity. 3. The role of multivalance. Immunochemistry. 1972; 9(3):325-40. DOI: 10.1016/0019-2791(72)90096-1. View

17.

Myerowitz R, Handzel Z, Scheerson R, Robbins J . Induction of Haemophilus influenzae type b capsular antibody in neonatal rabbits by gastrointestinal colonization with cross-reacting Escherichia coli. Infect Immun. 1973; 7(2):137-40. PMC: 422650. DOI: 10.1128/iai.7.2.137-140.1973. View

18.

Schneerson R, Robbins J . Induction of serum Haemophilus influenzae type B capsular antibodies in adult volunteers fed cross-reacting Escherichia coli 075:K100:H5. N Engl J Med. 1975; 292(21):1093-6. DOI: 10.1056/NEJM197505222922103. View

19.

Granoff D, Boies E, Munson Jr R . Immunogenicity of Haemophilus influenzae type b polysaccharide--diphtheria toxoid conjugate vaccine in adults. J Pediatr. 1984; 105(1):22-7. DOI: 10.1016/s0022-3476(84)80350-9. View

20.

LEPOW M, SAMUELSON J, Gordon L . Safety and immunogenicity of Haemophilus influenzae type B polysaccharide-diphtheria toxoid conjugate vaccine in adults. J Infect Dis. 1984; 150(3):402-6. DOI: 10.1093/infdis/150.3.402. View