Immune responsiveness in the neonatal period.
Abstract: The maintenance of pregnancy requires suppression of the maternal immune system which would naturally recognize the developing fetus as an allograft and seek to destroy it by mounting a Th1 regulated cytotoxic immune response. During pregnancy a range of soluble factors are produced by the placenta which switch maternal immune regulation towards a protective Th2 phenotype. These factors also influence the developing fetal immune system and all newborns initially have an immunological milieu skewed towards Th2 immunity. Vaccination during the neonatal period must therefore overcome the dual challenge of the inhibitory effect of maternally derived antibody and this natural Th2 regulatory environment. One means of overcoming these obstacles is by the use of adjuvant systems that can redirect the neonatal immune response towards an appropriate Th1 regulated reaction that affords protection from infectious disease. In this overview, experiments are described in which viral antigens incorporated into immune stimulatory complexes (ISCOMs) are able to induce immune responses with balanced Th1 and Th2 regulation in neonatal mice, as evidenced by the nature of the IgG subclass response and cytokine profile, and the induction of cytotoxic lymphocytes. ISCOM adjuvanted vaccines are able to induce similar protective immunity in the newborn of larger animal species including cattle, horses and dogs.
Publication Date: 2007-06-04 PubMed ID: 17548093DOI: 10.1016/j.jcpa.2007.04.008Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Review
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research paper explores how vaccines can overcome challenges due to maternal immune system suppression for protecting fetuses, which results in neonates having a Th2-dominant immune system. It proposes using immune stimulatory complexes (ISCOMs) as a vaccination adjuvant to balance both Th1 and Th2 immune responses in newborn mammals.
Th1 and Th2 Immune Responses
- The researchers point out that the maternal immune system naturally suppresses Th1 immune responses during pregnancy. Th1 responses are typically pro-inflammatory and cytotoxic, directing the immune system to destroy foreign cells.
- This suppression occurs to prevent the mother’s immune system from recognizing the fetus as foreign and destroying it.
- Due to factors produced by the placenta, the mother’s immune system is transitioned towards the Th2 phenotype which is non-cytotoxic and more geared towards maintaining the pregnancy.
- The developing fetus is influenced by these factors, thus neonates are also born with a Th2-skewed immune system.
Challenges with Neonatal Vaccination
- One of the main challenges with vaccinating newborns is their naturally suppressed Th1 immunity and dominant Th2 immunity. This can reduce the effectiveness of vaccinations that require a Th1 response to protect against infectious diseases.
- Moreover, the maternal antibodies passed on to the newborn can also land inhibitory effects on vaccinations provided during the neonatal period.
Proposed Solution: ISCOMs as a Vaccination Adjuvants
- In order to overcome these challenges, the researchers propose using immune stimulatory complexes (ISCOMs) as adjuvants in vaccines.
- An adjuvant is a substance that enhances the body’s immune response to an antigen. In this case, ISCOMs can be used to promote a balanced Th1 and Th2 immune response.
- Their study demonstrates this by incorporating viral antigens into ISCOMs and administering them to neonatal mice. They were able to induce a balanced Th1/Th2 immune response as shown by the IgG subclass response, cytokines produced, and the induction of cytotoxic lymphocytes.
- This suggests that ISCOMs could serve effectively as vaccine adjuvants to overcome the natural Th2-skew of the neonatal immune system and the inhibitory effect of maternal antibodies.
- This approach has also been shown to work in larger animal species like cattle, horses, and dogs, suggesting its potential broader application.
Cite This Article
APA
Morein B, Blomqvist G, Hu K.
(2007).
Immune responsiveness in the neonatal period.
J Comp Pathol, 137 Suppl 1, S27-S31.
https://doi.org/10.1016/j.jcpa.2007.04.008 Publication
Researcher Affiliations
- Department of Clinical Virology, Uppsala University, Sweden. bror.morein@telia.com
MeSH Terms
- Animals
- Animals, Newborn / immunology
- Animals, Newborn / physiology
- Antibody Formation / immunology
- Antibody Formation / physiology
- Antigens, Viral / immunology
- Cattle
- Dogs
- Horses
- ISCOMs / immunology
- Immune System / immunology
- Immune System / physiology
- Immunity, Maternally-Acquired / immunology
- Immunity, Maternally-Acquired / physiology
- Mice
- Viral Vaccines / immunology
Citations
This article has been cited 30 times.- Wirsching S, Machtakova M, Borgans F, Pretsch L, Fichter M, Cacicedo ML, Thérien-Aubin H, Landfester K, Gehring S. OVA-PEG-R848 nanocapsules stimulate neonatal conventional and plasmacytoid dendritic cells.. Front Pediatr 2022;10:966113.
- Singh G, Tucker EW, Rohlwink UK. Infection in the Developing Brain: The Role of Unique Systemic Immune Vulnerabilities.. Front Neurol 2021;12:805643.
- Sarfas C, White AD, Sibley L, Morrison AL, Gullick J, Lawrence S, Dennis MJ, Marsh PD, Fletcher HA, Sharpe SA. Characterization of the Infant Immune System and the Influence and Immunogenicity of BCG Vaccination in Infant and Adult Rhesus Macaques.. Front Immunol 2021;12:754589.
- Severance EG, Yolken RH. Role of Immune and Autoimmune Dysfunction in Schizophrenia.. Handb Behav Neurosci 2016;23:501-516.
- Maina TW, Grego EA, Boggiatto PM, Sacco RE, Narasimhan B, McGill JL. Applications of Nanovaccines for Disease Prevention in Cattle.. Front Bioeng Biotechnol 2020;8:608050.
- Wang A, Chao T, Ji Z, Xuan R, Liu S, Guo M, Wang G, Wang J. Transcriptome analysis reveals potential immune function-related regulatory genes/pathways of female Lubo goat submandibular glands at different developmental stages.. PeerJ 2020;8:e9947.
- Iwamoto J, Furukawa M. The estimation of duration of maternally-derived antibodies against Akabane, Aino, and Chuzan virus in calves by the receiver operating characteristic analysis.. J Vet Med Sci 2020 Nov 12;82(11):1614-1618.
- Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Bresson JL, Dusemund B, Gundert-Remy U, Kersting M, Lambré C, Penninks A, Tritscher A, Waalkens-Berendsen I, Woutersen R, Arcella D, Court Marques D, Dorne JL, Kass GE, Mortensen A. Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age.. EFSA J 2017 May;15(5):e04849.
- Sakala IG, Eichinger KM, Petrovsky N. Neonatal vaccine effectiveness and the role of adjuvants.. Expert Rev Clin Immunol 2019 Aug;15(8):869-878.
- Saso A, Kampmann B. Vaccine responses in newborns.. Semin Immunopathol 2017 Nov;39(6):627-642.
- Veazey RS, Lu Y, Xu H, Ziani W, Doyle-Meyers LA, Ratterree MS, Wang X. Maternal antibodies against tetanus toxoid do not inhibit potency of antibody responses to autologous antigen in newborn rhesus monkeys.. J Med Primatol 2018 Feb;47(1):35-39.
- Du Plessis N, Jacobs R, Gutschmidt A, Fang Z, van Helden PD, Lutz MB, Hesseling AC, Walzl G. Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis.. Eur J Immunol 2017 Jan;47(1):107-118.
- Yamaguchi T, Takizawa F, Fischer U, Dijkstra JM. Along the Axis between Type 1 and Type 2 Immunity; Principles Conserved in Evolution from Fish to Mammals.. Biology (Basel) 2015 Nov 17;4(4):814-59.
- Gasparini R, Panatto D, Bragazzi NL, Lai PL, Bechini A, Levi M, Durando P, Amicizia D. How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines.. J Immunol Res 2015;2015:189153.
- Mansoor F, Earley B, Cassidy JP, Markey B, Doherty S, Welsh MD. Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves.. BMC Vet Res 2015 Aug 21;11:220.
- Ostermann E, Macquin C, Krezel W, Bahram S, Georgel P. Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates.. Viruses 2015 May 6;7(5):2308-20.
- Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies.. Front Immunol 2014;5:446.
- Ostermann E, Macquin C, Bahram S, Georgel P. Use of in vivo imaging to monitor the progression of experimental mouse cytomegalovirus infection in neonates.. J Vis Exp 2013 Jul 6;(77):e50409.
- Hageman JH, Hooyenga P, Diersen-Schade DA, Scalabrin DM, Wichers HJ, Birch EE. The impact of dietary long-chain polyunsaturated fatty acids on respiratory illness in infants and children.. Curr Allergy Asthma Rep 2012 Dec;12(6):564-73.
- Kodama R, Okazaki T, Sato T, Iwashige S, Tanigawa Y, Fujishima J, Moriyama A, Yamashita N, Sasaki Y, Yoshikawa T, Kamimura Y, Maeda H. Age Difference in Morphology and Immunohistology inthe Thymus and Spleen in Crl:CD (SD) Rats.. J Toxicol Pathol 2012 Mar;25(1):55-61.
- Arnett AL, Garikipati D, Wang Z, Tapscott S, Chamberlain JS. Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector.. Front Microbiol 2011;2:220.
- Szczawinska-Poplonyk A. An overlapping syndrome of allergy and immune deficiency in children.. J Allergy (Cairo) 2012;2012:658279.
- Sanchez-Schmitz G, Levy O. Development of newborn and infant vaccines.. Sci Transl Med 2011 Jul 6;3(90):90ps27.
- Dimmitt RA, Staley EM, Chuang G, Tanner SM, Soltau TD, Lorenz RG. Role of postnatal acquisition of the intestinal microbiome in the early development of immune function.. J Pediatr Gastroenterol Nutr 2010 Sep;51(3):262-73.
- Muller WJ, Jones CA, Koelle DM. Immunobiology of herpes simplex virus and cytomegalovirus infections of the fetus and newborn.. Curr Immunol Rev 2010;6(1):38-55.
- Wagner B, Burton A, Ainsworth D. Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals.. Vet Res 2010 Jul-Aug;41(4):47.
- Costigan M, Moss A, Latremoliere A, Johnston C, Verma-Gandhu M, Herbert TA, Barrett L, Brenner GJ, Vardeh D, Woolf CJ, Fitzgerald M. T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity.. J Neurosci 2009 Nov 18;29(46):14415-22.
- Philbin VJ, Levy O. Developmental biology of the innate immune response: implications for neonatal and infant vaccine development.. Pediatr Res 2009 May;65(5 Pt 2):98R-105R.
- Madson DM, Patterson AR, Ramamoorthy S, Pal N, Meng XJ, Opriessnig T. Effect of porcine circovirus type 2 (PCV2) vaccination of the dam on PCV2 replication in utero.. Clin Vaccine Immunol 2009 Jun;16(6):830-4.
- Demirjian A, Levy O. Safety and efficacy of neonatal vaccination.. Eur J Immunol 2009 Jan;39(1):36-46.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
