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.
Highlights
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
It is possible that even if newborn B cells have adult-like expression of CD40, they are still be subject to alterations in signal transduction independent of any T follicular helper (Tfh)-dependent factors
While it remains unclear whether the relationship between Tfh and immunodominance in young infants will be the same as in adults, the success of Tfh stimulation for elicitation of antibody responses in young infants presents a promising avenue for future development of strategies to generate broadly protective Influenza A virus (IAV) vaccines
Summary
Infants must make the transition from the protected environment of the womb to the antigen-rich outside world. Influenza A virus (IAV) is a relatively common viral respiratory tract pathogen that exhibits higher rates of infection and leads to higher incidence of serious disease or secondary complications following primary infection of newborns and young infants [6,7,8] Compounding this increased susceptibility to infection and severe disease, the dampened newborn immune response poses significant challenges for the elicitation of protective immunity by vaccination [9]. In addition to lacking potency in the initial immune response, responses in young infants tend to be relatively transient, limiting the window of protection that is conferred even in the face of successful immune stimulation [10,11] Because of these barriers to vaccine efficacy, there is currently no IAV vaccine available to infants under 6 months of age [12,13]. ↑ initial proliferationAltered responses to TLR signaling despite similar levels of expression
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