16 research outputs found
Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.
Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity
Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.
Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine
Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants
The global burden of neonatal and infant mortality due to infection is
staggering, particularly in resource-poor settings. Early childhood vaccination
is one of the major interventions that can reduce this burden, but there are
specific limitations to inducing effective immunity in early life, including
impaired neonatal leukocyte production of Th1-polarizing cytokines to many
stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate
immune responses in infants may shed light on susceptibility to infection in
this vulnerable age group, and provide insights into TLR agonists as candidate
adjuvants for improved neonatal vaccines. As little is known about the leukocyte
responses of infants in resource-poor settings, we characterized production of
Th1-, Th2-, and anti-inflammatory- cytokines in response to agonists of TLRs 1-9
in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12
months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and
IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5,
and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that
also uniquely induced cord blood IFNγ production. For most agonists,
TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of
age. TLR8 agonists also induced the greatest production of the Th1-polarizing
cytokines TNFα and IFNγ throughout the first year of life, although the
relative responses to the single TLR8 agonist and the combined TLR7/8 agonist
changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most
agonists were robust at birth and remained stable through 12 months of age.
These observations provide fresh insights into the ontogeny of innate immunity
in African children, and may inform development of age-specific adjuvanted
vaccine formulations important for global health
Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules
Measles Virus Antibody Responses in Children Randomly Assigned to Receive Standard-Titer Edmonston-Zagreb Measles Vaccine at 4.5 and 9 Months of Age, 9 Months of Age, or 9 and 18 Months of Age
Viral vector malaria vaccines induce high-level T cell and antibody responses in West African children and infants
Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine
Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants
Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine