Understanding Antibody Responses in Early Life: Baby Steps towards Developing an Effective Influenza Vaccine

Abstract

The immune system of young infants is both quantitatively and qualitatively distinct from that of adults, with diminished responsiveness leaving these individuals vulnerable to infection. Because of this, young infants suffer increased morbidity and mortality from respiratory pathogens such as influenza viruses. The impaired generation of robust and persistent antibody responses in these individuals makes overcoming this increased vulnerability through vaccination challenging. Because of this, an effective vaccine against influenza viruses in infants under 6 months is not available. Furthermore, vaccination against influenza viruses is challenging even in adults due to the high antigenic variability across viral strains, allowing immune evasion even after induction of robust immune responses. This has led to substantial interest in understanding how specific antibody responses are formed to variable and conserved components of influenza viruses, as immune responses tend to strongly favor recognition of variable epitopes. Elicitation of broadly protective antibody in young infants, therefore, requires that both the unique characteristics of young infant immunity as well as the antibody immunodominance present among epitopes be effectively addressed. Here, we review our current understanding of the antibody response in newborns and young infants and discuss recent developments in vaccination strategies that can modulate both magnitude and epitope specificity of IAV-specific antibody.

Biomarkers detected in cord blood predict vaccine responses in young infants

“…Switched memory B cells develop quickly over the first 6 months of life and are maintained, with plasmablasts at their peak immediately after the battery of 6-month immunizations (29). The results indicate that the study cohort displayed the expected postimmunization patterns of B-cell development to allow for an assessment of the relationship between immune biomarkers and immunization responses in healthy infants (3,4,8,32). Multiple biomarkers (IL-21, sCD40L, BAFF, APRIL, IL-4, IL-17A, IL-22, IL-1b, and sCD163) were elevated at birth compared to 6 months of age.…”

State of pneumococcal vaccine immunity

“…The generation of Tfh cells and germinal center B cells is weaker in early age 39 , 42 and the suboptimal response to TD vaccines in infants is attributed to limited Tfh generation and germinal center B cell development. 43 Importantly, the details of TD antigen induced germinal center reaction in infants are not known. By using a neonatal mouse model, we studied the role of IL-6 in the generation of Tfh cells and germinal center B cells in response to TT conjugated pneumococcal serotype 14 CPS (PPS14-TT) vaccine.…”

Sex-Dependent Effects on Influenza-Specific Antibody Quantity and Neutralizing Activity following Vaccination of Newborn Non-Human Primates Is Determined by Adjuvants

“…Newborn infants were vaccinated in two cohorts, either nursery-reared or motherreared. These two cohorts were individually assessed, and we previously reported the effects of these adjuvants on the antibody response [21][22][23][24][25][26]. Although we had both males and females in each cohort, the number of animals in each vaccine group was inadequate to address the impact of sex.…”