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Review
. 2021 Feb 10:9:2515135520981516.
doi: 10.1177/2515135520981516. eCollection 2021.

Strategies for active and passive pediatric RSV immunization

Katherine M Eichinger  1 , Jessica L Kosanovich  2 , Madeline Lipp  3 , Kerry M Empey  4 , Nikolai Petrovsky  5
Affiliations
Review

Strategies for active and passive pediatric RSV immunization

Katherine M Eichinger et al. Ther Adv Vaccines Immunother. .

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide, with the most severe disease occurring in very young infants. Despite half a century of research there still are no licensed RSV vaccines. Difficulties in RSV vaccine development stem from a number of factors, including: (a) a very short time frame between birth and first RSV exposure; (b) interfering effects of maternal antibodies; and (c) differentially regulated immune responses in infants causing a marked T helper 2 (Th2) immune bias. This review seeks to provide an age-specific understanding of RSV immunity critical to the development of a successful pediatric RSV vaccine. Historical and future approaches to the prevention of infant RSV are reviewed, including passive protection using monoclonal antibodies or maternal immunization strategies versus active infant immunization using pre-fusion forms of RSV F protein antigens formulated with novel adjuvants such as Advax that avoid excess Th2 immune polarization.

Keywords: RSV; Respiratory Syncytial Virus; adjuvant; infant; neonate; vaccine.

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Conflict of interest statement

Conflict of interest: Nikolai Petrovsky is affiliated with Vaxine Pty Ltd, which owns the Advax adjuvant technology. Katherine M. Eichinger, Jessica L. Kosanovich, Madeline Lipp, and Kerry M. Empey have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Key facts on respiratory syncytial virus (RSV).
Figure 2.
Figure 2.
Differences in immune responses to RSV between infants and adults. Data from RSV-infected infants and animal models demonstrate infant immune responses are manifested by reduced anti-viral type I/II interferon (IFN) production and increased T helper (Th)-2 and anti-inflammatory cytokine production when compared to adults. The adaptive immune response of infants is characterized by reduced activation and IgG class switching of B cells with higher production of IgM compared to IgG from a reduced plasma cell population. Neonatal T-cell populations are also altered and demonstrate reduced proliferation, decreased expression of co-stimulatory markers, and a higherinterleukin (IL)-4/IL-17A to IFNγ ratio BAFF, B-cell activating factor of the tumor necrosis factor family; BCMA, B-cell maturation antigen; mTOR, mammalian target of rapamycin; pDC, plasmacytoid dendritic cells; RSV, respiratory syncytial virus; TACI, transmembrane activator and calcium-modulating cyclophilin ligand interactor.
Figure 3.
Figure 3.
Timeline of RSV - vaccine and monoclonal antibody development. RSV, respiratory syncytial virus.
See this image and copyright information in PMC

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