Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure.
ABSTRACT A serologic study was made in 34 children immunized against measles at the age of 12 months. Using a sensitive virus neutralization test, it was found that many of the children had pre-existing maternal antibody to measles virus. Children with high pre-existing antibody titers failed to seroconvert. Children with lower pre-existing antibody titers seroconverted, but the resulting antibody titer was significantly lower than in children without pre-existing antibody titer. The results of this study demonstrate a probably mechanism for measles vaccine failure in 12-month-old children and support the recommendation of the Public Health Service Advisory Committee on Immunization Practices to postpone measles vaccination to 15 months of age.
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ABSTRACT: Human newborns and infants are bombarded with multiple pathogens on leaving the sterile intra-uterine environment, and yet have suboptimal innate immunity and limited immunological memory, thus leading to increased susceptibility to infections in early life. They are thus the target age group for a host of vaccines against common bacterial and viral pathogens. They are also the target group for many vaccines in development, including those against tuberculosis (TB), malaria, and HIV infection. However, neonatal and infant responses too many vaccines are suboptimal, and in the case of the polysaccharide vaccines, it has been necessary to develop the alternative conjugated formulations in order to induce immunity in early life. Immunoregulatory factors are an intrinsic component of natural immunity necessary to dampen or control immune responses, with the caveat that they may also decrease immunity to infections or lead to chronic infection. This review explores the key immunoregulatory factors at play in early life, with a particular emphasis on regulatory T cells (Tregs). It goes on to explore the role that Tregs play in limiting vaccine immunogenicity, and describes animal and human studies in which Tregs have been depleted in order to enhance vaccine responses. A deeper understanding of the role that Tregs play in limiting or controlling vaccine-induced immunity would provide strategies to improve vaccine immunogenicity in this critical age group. New adjuvants and drugs are being developed that can transiently suppress Treg function, and their use as part of human vaccination strategies against infections is becoming a real prospect for the future.Frontiers in Microbiology 09/2014; 5:477. DOI:10.3389/fmicb.2014.00477 · 3.94 Impact Factor
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ABSTRACT: ABSTRACT This study was designed to assess the seroconversion rate of measles vaccine among infants receiving measles immunization in Ilorin, Nigeria. The pre- and post measles vaccination sera of the children were tested using the Haemagglutination Inhibition test. The measles vaccines administered at the immunization centre were also tested for their potency using in-vitro titration method. Only 286 (71.5%) of the vacinees returned to give post- vaccination samples. All the infants screened had low pre -vaccination measles antibody titers. Thirty one (8.0%) of the infants had measles prior to vaccination. The seroconversion pattern showed that 196 (68.6%) of the infants developed protective antibody titers. The low seroconversion rate obtained was due to low vaccine potency with titers ranging between log10(-1.0) - log10(-2.25) TCID/per dose. This was beside other non-specific antiviral substances exhibited virus neutralizing activity. Only 3(50%) of the 6 vaccine vials tested had virus titers of log10(-3.25) to log10(-3.5), which fell above the cut-off point recommended by the World Health Organization for measles vaccines. The sero-conversion rate of 68.6% observed among vaccinees is far lower than the immunity level of 95% required stopping measles transmission in an endemic community. Failure of 31.4% of these infants to sero-convert post vaccination can be attributed partly to administration of sub-potent vaccines. There is need for improvement and maintenance of effective vaccine cold chain system in Nigeria. There is need also for periodic monitoring of post vaccination antibody titers as well as vaccine potency status in order to ensure development of protective seroconversion rates.Journal of Immunoassay and Immunochemistry 05/2014; DOI:10.1080/15321819.2014.920713 · 0.73 Impact Factor
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ABSTRACT: ABSTRACT Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4(+) and CD8(+) T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4(+) and CD8(+) T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA. IMPORTANCE The components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from rash or viremia when challenged with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized animals. Thus, T-cell immunity did not protect from infection or acute disease but facilitated virus clearance during recovery. These studies demonstrate the importance and independent roles of T cells and antibody in protection and recovery from measles.mBio 02/2014; 5(2). DOI:10.1128/mBio.01047-14 · 6.88 Impact Factor