The Vi Conjugate Typhoid Vaccine Is Safe, Elicits Protective Levels of IgG Anti-Vi, and Is Compatible with Routine Infant Vaccines

Abstract

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2-to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccinerelated serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of >3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of >3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.Typhoid fever remains a common, serious, and difficult-totreat disease throughout the world, including Vietnam (6,20). In the Mekong Delta region, the incidence of typhoid in 2-to 4-year-olds is similar to that in school-age children (20). Similar findings have been reported in other Asian countries (4,24,30). Typhoid is still a difficult diagnosis to make. Affected infants are often unrecognized because of atypical presentations, and it is often difficult to obtain adequate amounts of blood for culture, the most reliable available diagnostic test, which still identifies only 50% of cases diagnosed by bone marrow culture (the most sensitive assay) (9, 11). Lastly, it has not been possible to mobilize personnel and vaccines to immunize the population during outbreaks of typhoid (22,34). These data indicate that effective vaccination for typhoid should be administered as part of the routine immunization of infants.The three licensed typhoid vaccines (parenteral inactivated whole-cell vaccine, oral attenuated Salmonella enterica serovar Typhi Ty21a, and parenteral Vi polysaccharide) confer approximately 70% protection to older children and adults and do not protect young children (1,13,18). We planned to develop a typhoid vaccine to administer to infants as part of their ...

Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

“…More immunogenic live attenuated strains and Vi conjugate vaccines presently under development are expected to overcome the limitations of the current licensed typhoid vaccines (9)(10)(11)(12)(13). Not surprisingly, analogous strategies are being pursued to develop live oral and conjugate paratyphoid A and NTS vaccines (14)(15)(16)(17)(18).…”

Capsular polysaccharide vaccine for Group BNeisseria meningitidis,Escherichia coliK1, andPasteurella haemolyticaA2

“…It seems improbable that such a common surface structure could be the target of autoimmune serum antibodies. In this essay, we review the data that allow us to propose that (2→8)-α-Neu5Ac conjugates will be as safe and effective as the polysaccharide protein conjugate vaccines for the other four meningococcal serogroups, Haemophilus influenzae type b, pneumococci, and Salmonella typhi (Vi) (1,14,15).…”

Thermostable Cross-Protective Subunit Vaccine against Brucella Species

“…There have also been successes on the use of their components to induce immunity, namely, key proteins, but some successful PS subunit vaccines have been those against Haemophilus influenzae, Neisseria meningitidis, Salmonella enterica serovar Typhi, and Streptococcus pneumoniae (19,20). The PS of these vaccines have been conjugated to proteins to enhance antibody titers (21) and T-cell memory responses (22).…”