The effect of meningococcal vaccines on new generation of systemic inflammatory markers in children

Abstract

Aim:Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of meningococcal infections. In this study, in order to support the appropriate use of various MVs in the prevention of meningococcal meningitis (MM), the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in < 5-year-old children were investigated.

Methods:A total of 464 healthy children were included in this study. The data of those who received the first 2 doses at 2-month intervals and the next dose between 8–12 months were included. Nimenrix^® (Pfizer) administered as a single dose to children from 12 months of age. Bexsero^® (GSK) was administered as 2 + 1 doses under 2 years of age and 2 doses 2 months apart over 2 years of age. Neutrophil, lymphocyte, monocyte, platelet counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIR-I), and systemic immune inflammation index (SII) were evaluated.

Results:Of the 464 participants, 58.2% were male, with a mean age of 3.81 years, and both sex ratios and ages were similar across the Nimenrix and Bexsero groups. The laboratory and inflammatory parameters of the two vaccine groups were similar. In both vaccine groups, changes in laboratory parameters before and 3-months after vaccination were similar. The changes in laboratory parameters over time between vaccine groups and their interactions were not significant.

Conclusions:The NLR, dNLR, PLR, SIR-I, and SII are useful biomarkers indicating the inflammatory response of Nimenrix and Bexsero vaccines. Inflammatory markers can be used as both a safety endpoint and a protection endpoint for MVs (Nimenrix and Bexsero). However, further studies involving larger patient cohorts as well as detailed laboratory data on specific markers of inflammation are needed to draw comprehensive conclusions regarding the inflammatory response following vaccination.

Keywords

Meningococcal vaccine / Nimenrix / Bexsero / neutrophil-to-lymphocyte ratio / platelet-to-lymphocyte ratio / systemic inflammation response index / systemic immune inflammation index

References

[1] Nadel S, Ninis N. Invasive Meningococcal Disease in the Vaccine Era. Front Pediatr. 2018; 6: 321.

[2] Rouphael NG, Stephens DS. Neisseria meningitidis: biology, microbiology, and epidemiology . Methods Mol Biol. 2012; 799: 1-20.

[3] Ölüm İstatistikleri, 2017 [Internet]. Ankara: Türkiye İstatistik Kurumu; [cited 2018 Jun 7]. Available from: https://data.tuik.gov.tr/Bulten/Index?p=Olum-Istatistikleri-2017-27592

[4] Banzhoff A. Multicomponent meningococcal B vaccination (4CMenB) of adolescents and college students in the United States. Ther Adv Vaccines. 2017; 5: 3-14.

[5] Bagwe P, Bajaj L, Gala R, Zughaier SM, Uddin MN, D’Souza MJ. Meningococcal Vaccines: Challenges and Prospects. Vaccines (Basel). 2020; 8: 738.

[6] Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. N Engl J Med. 2001; 344: 1378-88.

[7] Di Pietro GM, Biffi G, Castellazzi ML, Tagliabue C, Pinzani R, Bosis S, et al. Meningococcal Disease in Pediatric Age: A Focus on Epidemiology and Prevention. Int J Environ Res Public Health. 2022; 19: 4035.

[8] Millar BC, Banks L, Bourke TW, Cunningham M, Dooley J, Elshibly S, et al. Meningococcal Disease Section 3: Diagnosis and Management: MeningoNI Forum. Ulster Med J. 2018; 87: 94-8.

[9] Runde TJ, Anjum F, Hafner JW. Bacterial Meningitis. Treasure Island (FL): StatPearls Publishing; 2025.

[10] Hrishi AP, Sethuraman M. Cerebrospinal Fluid (CSF) Analysis and Interpretation in Neurocritical Care for Acute Neurological Conditions. Indian J Crit Care Med. 2019; 23: S115-9.

[11] Gioia S, Piazze J, Anceschi MM, Cerekja A, Alberini A, Giancotti A, et al. Mean platelet volume: association with adverse neonatal outcome. Platelets. 2007; 18: 284-8.

[12] Kim NY, Chun DH, Kim SY, Kim NK, Baik SH, Hong JH, et al. Prognostic Value of Systemic Inflammatory Indices, NLR, PLR, and MPV, for Predicting 1-Year Survival of Patients Undergoing Cytoreductive Surgery with HIPEC. J Clin Med. 2019; 8: 589.

[13] Korniluk A, Koper-Lenkiewicz OM, Kamińska J, Kemona H, Dymicka-Piekarska V. Mean Platelet Volume (MPV): New Perspectives for an Old Marker in the Course and Prognosis of Inflammatory Conditions. Mediators Inflamm. 2019; 2019: 9213074.

[14] Mihai A, Caruntu A, Opris-Belinski D, Jurcut C, Dima A, Caruntu C, et al. The Predictive Role of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocytes-to-Lymphocyte Ratio (MLR) and Gammaglobulins for the Development of Cutaneous Vasculitis Lesions in Primary Sjögren’s Syndrome. J Clin Med. 2022; 11: 5525.

[15] Lee JS, Kim NY, Na SH, Youn YH, Shin CS. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore). 2018; 97: e11138.

[16] Kimberlin DW, Brady MT, Jackson MA, editors. Meningococcal Infections. Red Book (2018): Report of the Committee on Infectious Diseases. 31st ed. Itasca: American Academy of Pediatrics; 2018. pp. 550-61.

[17] Robinson JL. Update on invasive meningococcal vaccination for Canadian children and youth. Paediatr Child Health. 2018; 23: e1-4.

[18] Child and Adolescent Immunization Schedule by Age [Internet]. U.S. Centers for Disease Control and Prevention; [cited 2019 Nov 12]. Available from: https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html

[19] Vaccine schedules in all countries in the EU/EEA [Internet]. European Centre for Disease Prevention and Control (ECDC); c2025 [2019 Nov 12]. Available from: https://vaccine-schedule.ecdc.europa.eu/

[20] Wilkins AL, Snape MD. Emerging clinical experience with vaccines against group B meningococcal disease. Vaccine. 2018; 36: 5470-6.

[21] Ladhani SN, Giuliani MM, Biolchi A, Pizza M, Beebeejaun K, Lucidarme J, et al. Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England . Emerg Infect Dis. 2016; 22: 309-11.

[22] Baxter R, Baine Y, Ensor K, Bianco V, Friedland LR, Miller JM. Immunogenicity and safety of an investigational quadrivalent meningococcal ACWY tetanus toxoid conjugate vaccine in healthy adolescents and young adults 10 to 25 years of age. Pediatr Infect Dis J. 2011; 30: e41-8.

[23] Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019; 4: 39.

[24] Dull PM, McIntosh ED. Meningococcal vaccine development - from glycoconjugates against MenACWY to proteins against MenB - potential for broad protection against meningococcal disease. Vaccine. 2012; 30 Suppl 2: B18-25.

[25] Nadel S. Prospects for eradication of meningococcal disease. Arch Dis Child. 2012; 97: 993-8.

[26] McQuaid F, Snape MD, John TM, Kelly S, Robinson H, Yu LM, et al. Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months. CMAJ. 2015; 187: E215-23.

[27] Stefanizzi P, Di Lorenzo A, Martinelli A, Moscara L, Stella P, Ancona D, et al. Adverse events following immunization (AEFIs) with anti-meningococcus type B vaccine (4CMenB): Data of post-marketing active surveillance program. Apulia Region (Italy), 2019-2023. Vaccine. 2023; 41: 7096-102.

[28] Stefanizzi P, Bianchi FP, Spinelli G, Amoruso F, Ancona D, Stella P, et al. Postmarketing surveillance of adverse events following meningococcal B vaccination: data from Apulia Region, 2014-19. Hum Vaccin Immunother. 2022; 18: 1-6.

[29] Esposito S, Prymula R, Zuccotti GV, Xie F, Barone M, Dull PM, et al. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II). Hum Vaccin Immunother. 2014; 10: 2005-14.

[30] Şener G, Bayrak T, Coşkun C, Bayrak A. Neutrophil Lymphocyte Ratio, Monocyte Lymphocyte Ratio, Platelet Lymphocyte Ratio in Covid-19 Patients. Clin Lab. 2022; 68.

[31] Parthasarathi A, Padukudru S, Arunachal S, Basavaraj CK, Krishna MT, Ganguly K, et al. The Role of Neutrophil-to-Lymphocyte Ratio in Risk Stratification and Prognostication of COVID-19: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2022; 10: 1233.

[32] Shusterman E, Prozan L, Ablin JN, Weiss-Meilik A, Adler A, Choshen G, et al. Neutrophil-to-lymphocyte ratio trend at admission predicts adverse outcome in hospitalized respiratory syncytial virus patients. Heliyon. 2023; 9: e16482.

[33] Terradas R, Grau S, Blanch J, Riu M, Saballs P, Castells X, et al. Eosinophil count and neutrophil-lymphocyte count ratio as prognostic markers in patients with bacteremia: a retrospective cohort study. PLoS One. 2012; 7: e42860.

[34] Wang PH, Lin SY, Liou HH, Chen CC, Shu CC, Lee CY, et al. Protective Effect of BCG and Neutrophil-to-Lymphocyte Ratio on Latent Tuberculosis in End Stage Renal Disease. Infect Dis Ther. 2023; 12: 1907-20.

[35] Wang S, Wan Y, Zhang W. The Clinical Value of Systemic Immune Inflammation Index (SII) in Predicting the Severity of Hospitalized Children with Mycoplasma Pneumoniae Pneumonia: A Retrospective Study. Int J Gen Med. 2024; 17: 935-42.

[36] Okuyan O, Elgormus Y, Sayili U, Dumur S, Isık OE, Uzun H. The Effect of Virus-Specific Vaccination on Laboratory Infection Markers of Children with Acute Rotavirus-Associated Acute Gastroenteritis. Vaccines (Basel). 2023; 11: 580.

[37] McDade TW, Borja JB, Kuzawa CW, Perez TL, Adair LS. C-reactive protein response to influenza vaccination as a model of mild inflammatory stimulation in the Philippines. Vaccine. 2015; 33: 2004-8.

[38] Ferlito C, Visco V, Biselli R, Cattaruzza MS, Carreras G, Salerno G, et al. Safety of Multiple Vaccinations and Durability of Vaccine-Induced Antibodies in an Italian Military Cohort 5 Years after Immunization. Biomedicines. 2021; 10: 6.