Abstract
Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children. Efficacious vaccination has been a longstanding goal in neonates. Due to immaturity of the neonatal immune system, vaccination has shown limited success in stimulating the neonatal endogenous immune system. Advances in the understanding of neonatal immunology have resulted in renewed development of neonatal vaccination. In this article, we review recent advances in neonatal anti-RSV vaccination strategies, including active and passive vaccination approaches, with emphasis on the effect of maternal neutralizing antibody and the role of maternal antibody in neonatal immune modulations. Recent reports in a variety of antiviral vaccine animal models have shown that maternal antibody, different from conventional vaccination, plays an immune modulatory role in the newborn immune system. Active immunization of the pregnant mother and the offspring can effectively stimulate and maintain potent neonatal immune responses, including an endogenous cytotoxic response and neutralizing antibody generation. The induced newborn endogenous antiviral immunity can last up to 6 months, and effectively blunt viral replication. Immune complexes, formed from the integral binding of the maternal neutralizing antibody and viral vaccine antigen, may play an important role in the maternal antibody-mediated neonatal immune response. The underlying mechanisms and future perspectives are discussed.
Similar content being viewed by others
References
Abrahamson D R, Powers A, Rodewald R (1979). Intestinal absorption of immune complexes by neonatal rats: a route of antigen transfer from mother to young. Science, 206(4418): 567–569
Adkins B, Chun K, Hamilton K, Nassiri M (1996). Naive murine neonatal T cells undergo apoptosis in response to primary stimulation. J Immunol, 157(4): 1343–1349
Aiuti F, Mezzaroma I (2006). Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev, 8(2): 88–97
Anderson K, Rusterholz C, Månsson R, Jensen C T, Bacos K, Zandi S, Sasaki Y, Nerlov C, Sigvardsson M, Jacobsen S E (2007). Ectopic expression of PAX5 promotes maintenance of biphenotypic myeloid progenitors coexpressing myeloid and B-cell lineage-associated genes. Blood, 109(9): 3697–3705
Bachmann MF, Hunziker L, Zinkernagel RM, Storni T, Kopf M (2004). Maintenance of memory CTL responses by T helper cells and CD40-CD40 ligand: antibodies provide the key. Eur J Immunol, 34(2): 317–326
Blomqvist G A, Lövgren-Bengtsson K, Morein B (2003). Influence of maternal immunity on antibody and T-cell response in mice. Vaccine, 21(17–18): 2022–2031
Bueno S M, González P A, Cautivo K M, Mora J E, Leiva E D, Tobar H E, Fennelly G J, Eugenin E A, Jacobs WR Jr, Riedel C A, Kalergis A M (2008). Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG. Proc Natl Acad Sci USA, 105(52): 20822–20827
Buraphacheep W, Sullender W M (1997). The guinea pig as a model for the study of maternal immunization against respiratory syncytial virus infections in infancy. J Infect Dis, 175(4): 935–938
Cervenak J, Bender B, Schneider Z, Magna M, Carstea B V, Liliom K, Erdei A, Bosze Z, Kacskovics I (2011). Neonatal FcR overexpression boosts humoral immune response in transgenic mice. J Immunol, 186(2): 959–968
Connors M, Collins P L, Firestone C Y, Sotnikov A V, Waitze A, Davis A R, Hung P P, Chanock R M, Murphy B R (1992). Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia-RSV recombinants or RSV. Vaccine, 10(7): 475–484
Devey M E, Steward M W (1980). The induction of chronic antigenantibody complex disease in selectively bred mice producing either high or low affinity antibody to protein antigens. Immunology, 41(2): 303–311
Elrefaei M, McElroy M D, Preas C P, Hoh R, Deeks S, Martin J, Cao H (2004). Central memory CD4+ T cell responses in chronic HIV infection are not restored by antiretroviral therapy. J Immunol, 173(3): 2184–2189
Etchart N, Baaten B, Andersen S R, Hyland L, Wong S Y, Hou S (2006). Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge. Eur J Immunol, 36(5): 1136–1144
Franki S N, Steward K K, Betting D J, Kafi K, Yamada R E, Timmerman J M (2007). Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo. Blood, 111(3): 1504–1511
Gros L, Dreja H, Fiser A L, Plays M, Pelegrin M, Piechaczyk M (2005). Induction of long-term protective antiviral endogenous immune response by short neutralizing monoclonal antibody treatment. J Virol, 79(10): 6272–6280
Gros L, Pelegrin M, Michaud H A, Bianco S, Hernandez J, Jacquet C, Piechaczyk M (2008). Endogenous cytotoxic T-cell response contributes to the long-term antiretroviral protection induced by a short period of antibody-based immunotherapy of neonatally infected mice. J Virol, 82(3): 1339–1349
Gros L, Pelegrin M, Plays M, Piechaczyk M (2006). Efficient mother-tochild transfer of antiretroviral immunity in the context of preclinical monoclonal antibody-based immunotherapy. J Virol, 80(20): 10191–10200
Haigwood N L, Montefiori D C, Sutton W F, McClure J, Watson A J, Voss G, Hirsch VM, Richardson B A, Letvin N L, Hu S L, Johnson P R (2004). Passive immunotherapy in simian immunodeficiency virus-infected macaques accelerates the development of neutralizing antibodies. J Virol, 78(11): 5983–5995
Hamano Y, Arase H, Saisho H, Saito T (2000). Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses. J Immunol, 164(12): 6113–6119
Hancock G E, Speelman D J, Heers K, Bortell E, Smith J, Cosco C (1996). Generation of atypical pulmonary inflammatory responses in BALB/c mice after immunization with the native attachment (G) glycoprotein of respiratory syncytial virus. J Virol, 70(11): 7783–7791
Hazenbos W L, Heijnen I A, Meyer D, Hofhuis F M, Renardel de Lavalette C R, Schmidt R E, Capel P J, van de Winkel J G, Gessner J E, van den Berg T K, Verbeek J S (1998). Murine IgG1 complexes trigger immune effector functions predominantly via Fc gamma RIII (CD16). J Immunol, 161(6): 3026–3032
Hessell A J, Hangartner L, Hunter M, Havenith C E, Beurskens F J, Bakker J M, Lanigan C M, Landucci G, Forthal D N, Parren P W, Marx P A, Burton D R (2007). Fc receptor but not complement binding is important in antibody protection against HIV. Nature, 449(7158): 101–104
Heyman B (2000). Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu Rev Immunol, 18(1): 709–737
Hussell T, Baldwin C J, O’Garra A, Openshaw P J (1997). CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection. Eur J Immunol, 27(12): 3341–3349
Jakob T, Walker P S, Krieg A M, Udey M C, Vogel J C (1998). Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA. J Immunol, 161(6): 3042–3049
Kim HW, Canchola J G, Brandt C D, Pyles G, Chanock R M, Jensen K, Parrott R H (1969). Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol, 89(4): 422–434
Lee H H, Hoeman C M, Hardaway J C, Guloglu F B, Ellis J S, Jain R, Divekar R, Tartar D M, Haymaker C L, Zaghouani H (2008). Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity. J Exp Med, 205(10): 2269–2280
Lu L, Palaniyandi S, Zeng R, Bai Y, Liu X, Wang Y, Pauza C D, Roopenian D C, Zhu X (2011). A neonatal Fc receptor-targeted mucosal vaccine strategy effectively induces HIV-1 antigen-specific immunity to genital infection. J Virol, 85(20): 10542–10553
Mapletoft J W, Latimer L, Babiuk L A, van Drunen Littel-van den Hurk S (2010). Intranasal immunization of mice with a bovine respiratory syncytial virus vaccine induces superior immunity and protection compared to those by subcutaneous delivery or combinations of intranasal and subcutaneous prime-boost strategies. Clin Vaccine Immunol, 17(1): 23–35
Mejías A, Ramilo O (2008). Review of palivizumab in the prophylaxis of respiratory syncytial virus (RSV) in high-risk infants. Biologics, 2(3): 433–439
Michaud H A, Gomard T, Gros L, Thiolon K, Nasser R, Jacquet C, Hernandez J, Piechaczyk M, Pelegrin M (2010). A crucial role for infected-cell/antibody immune complexes in the enhancement of endogenous antiviral immunity by short passive immunotherapy. PLoS Pathog, 6(6): e1000948
Mozdzanowska K, Feng J, Gerhard W (2003). Virus-neutralizing activity mediated by the Fab fragment of a hemagglutinin-specific antibody is sufficient for the resolution of influenza virus infection in SCID mice. J Virol, 77(15): 8322–8328
Pinschewer D D, Perez M, Jeetendra E, Bächi T, Horvath E, Hengartner H, Whitt M A, de la Torre J C, Zinkernagel R M (2004). Kinetics of protective antibodies are determined by the viral surface antigen. J Clin Invest, 114(7): 988–993
Reuman P D, Keely S P, Schiff G M, Gamble J N (1991). Similar subclass antibody responses after intranasal immunization with UVinactivated RSV mixed with cholera toxin or live RSV. J Med Virol, 35(3): 192–197
Schuurhuis D H, van Montfoort N, Ioan-Facsinay A, Jiawan R, Camps M, Nouta J, Melief C J, Verbeek J S, Ossendorp F (2006). Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine. J Immunol, 176(8): 4573–4580
Siegrist C A, Barrios C, Martinez X, Brandt C, Berney M, Córdova M, Kovarik J, Lambert P H (1998). Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice. Eur J Immunol, 28(12): 4138–4148
Singleton R, Etchart N, Hou S, Hyland L (2003). Inability to evoke a long-lasting protective immune response to respiratory syncytial virus infection in mice correlates with ineffective nasal antibody responses. J Virol, 77(21): 11303–11311
Srikiatkhachorn A, Braciale T J (1997a). Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. J Exp Med, 186(3): 421–432
Srikiatkhachorn A, Braciale T J (1997b). Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection. J Virol, 71(1): 678–685
Victor J R, Muniz B P, Fusaro A E, de Brito C A, Taniguchi E F, Duarte A J, Sato M N (2010). Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells. BMC Immunol, 11(1): 11
Villinger F, Mayne A E, Bostik P, Mori K, Jensen P E, Ahmed R, Ansari A A (2003). Evidence for antibody-mediated enhancement of simian immunodeficiency virus (SIV) Gag antigen processing and cross presentation in SIV-infected rhesus macaques. J Virol, 77(1): 10–24
Wu Y, Sukumar S, El Shikh M E, Best A M, Szakal A K, Tew J G (2008). Immune complex-bearing follicular dendritic cells deliver a late antigenic signal that promotes somatic hypermutation. J Immunol, 180(1): 281–290
Yoshida M, Claypool S M, Wagner J S, Mizoguchi E, Mizoguchi A, Roopenian D C, Lencer W I, Blumberg R S (2004). Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity, 20(6): 769–783
Zaghouani H, Hoeman C M, Adkins B (2009). Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol, 30(12): 585–591
Zeng R, Qi X, Gong W, Mei X, Wei L, Ma C, Yin X (2007). Longlasting balanced immunity and protective efficacy against respiratory syncytial virus in mice induced by a recombinant protein G1F/M2. Vaccine, 25(42): 7422–7428
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jiang, Z., Fisher, E.M. & Jiang, J. Neonatal vaccination against respiratory syncytial virus infection. Front. Biol. 7, 227–232 (2012). https://doi.org/10.1007/s11515-012-1223-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11515-012-1223-1