期刊论文详细信息
BMC Infectious Diseases
Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees
Martha Torres3  Eduardo Sada3  Lourdes Garcia-Garcia1  Marcela Muñoz-Torrico3  Ma Eugenia Manjarrez2  Silvia Guzman-Beltran3  Carmen Sarabia3  Claudia Carranza3  Fernando Hernández-Sánchez3  Esmeralda Juárez3  Yolanda Gonzalez3  Ma Teresa Herrera3 
[1] Centro de Investigacion sobre Enfermedades Infecciosas, Instituto Nacional de Salud Publica, Cuernavaca, Mexico;Department of Virology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, Mexico City 14080, Mexico;Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, Mexico City 14080, Mexico
关键词: Humoral response;    Proliferation;    Cellular response;    Vaccine;    H1N1;    Pandemic influenza;   
Others  :  1145385
DOI  :  10.1186/1471-2334-13-544
 received in 2013-06-18, accepted in 2013-11-04,  发布年份 2013
PDF
【 摘 要 】

Background

The efficacy of the H1N1 influenza vaccine relies on the induction of both humoral and cellular responses. This study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza A/H1N1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine.

Methods

Sixty healthy workers from a respiratory disease hospital were recruited. Sera and peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 month after vaccination with a non-adjuvanted monovalent 2009 H1N1 vaccine (Influenza A (H1N1) 2009 Monovalent Vaccine Panenza, Sanofi Pasteur). Antibody titers against the pandemic A/H1N1 influenza virus were measured via hemagglutination inhibition (HI) and microneutralization assays. Antibodies against the seasonal HA1 were assessed by ELISA. The frequency of IFN-γ-producing cells as well as CD4+ and CD8+ T cell proliferation specific to the pandemic virus A/H1N peptides, seasonal H1N1 peptides and seasonal H3N2 peptides were assessed using ELISPOT and flow cytometry.

Results

At baseline, 6.7% of the subjects had seroprotective antibody titers. The seroconversion rate was 48.3%, and the seroprotection rate was 66.7%. The geometric mean titers (GMTs) were significantly increased (from 6.8 to 64.9, p < 0.05). Forty-nine percent of the subjects had basal levels of specific IFN-γ-producing T cells to the pandemic A/H1N1 peptides that were unchanged post-vaccination. CD4+ T cell proliferation in response to specific pandemic A/H1N1 virus peptides was also unchanged; in contrast, the antigen-specific proliferation of CD8+ T cells significantly increased post-vaccination.

Conclusion

Our results indicate that a cellular immune response that is cross-reactive to pandemic influenza antigens may be present in populations exposed to the circulating seasonal influenza virus prior to pandemic or seasonal vaccination. Additionally, we found that the pandemic vaccine induced a significant increase in CD8+ T cell proliferation.

【 授权许可】

   
2013 Herrera et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150402073041568.pdf 1498KB PDF download
Figure 4. 43KB Image download
Figure 3. 60KB Image download
Figure 2. 79KB Image download
Figure 1. 60KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, Miller MA: Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med 2009, 361(7):674-679.
  • [2]Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, Dawson G, Hu W, Leggio C, Washington D, et al.: Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med 2009, 361(25):2405-2413.
  • [3]Nolan T, McVernon J, Skeljo M, Richmond P, Wadia U, Lambert S, Nissen M, Marshall H, Booy R, Heron L, et al.: Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial. JAMA 2010, 303(1):37-46.
  • [4]Wu J, Li W, Wang HQ, Chen JT, Lv M, Zhou JC, Liang XF, Fang HH, Liu Y, Liu LY, et al.: A rapid immune response to 2009 influenza A(H1N1) vaccines in adults: a randomized, double-blind, controlled trial. J Infect Dis 2010, 202(5):675-680.
  • [5]Virus strains recommended by the World Health Organization for the development of the influenza A (H1N1) vaccines. http://www.who.int/csr/resources/publications/swineflu/2009_05_27_X179Aa.pdf webcite
  • [6]Zhou Y, Ng DM, Seto WH, Ip DK, Kwok HK, Ma ES, Ng S, Lau LL, Peiris JS, Cowling BJ: Seroprevalence of Pandemic H1N1 Antibody among Health Care Workers in Hong Kong Following Receipt of Monovalent 2009 H1N1 Influenza Vaccine. PloS One 2011, 6(11):e27169.
  • [7]Phongsamart W, Sirisanthana V, Wittawatmongkol O, Maleesatharn A, Sudjaritruk T, Chearskul P, Aurpibul L, Sirisanthana T, Chokephaibulkit K: Immunogenicity and safety of monovalent influenza A (H1N1) 2009 in HIV-infected Thai children. Vaccine 2011, 29(47):8705-8711.
  • [8]Van der Vliet D, Pepin S, Lambert M, Fauchoux N, Donazzolo Y, Dupuy M, Dakowski C, Denis M: Similar immunogenicity of the A/H1N1 2009 pandemic influenza strain when used as a monovalent or a trivalent vaccine. Hum Vaccin 2010, 6(10):823-828.
  • [9]Plennevaux E, Blatter M, Cornish MJ, Go K, Kirby D, Wali M, Reeves-Hoche MK, Denis M: Influenza A (H1N1) 2009 two-dose immunization of US children: an observer-blinded, randomized, placebo-controlled trial. Vaccine 2011, 29(8):1569-1575.
  • [10]Thomas PG, Keating R, Hulse-Post DJ, Doherty PC: Cell-mediated protection in influenza infection. Emerg Infect Dis 2006, 12(1):48-54.
  • [11]Brown LE, Kelso A: Prospects for an influenza vaccine that induces cross-protective cytotoxic T lymphocytes. Immunol Cell Biol 2009, 87(4):300-308.
  • [12]Schanen BC, De Groot AS, Moise L, Ardito M, McClaine E, Martin W, Wittman V, Warren WL, Drake DR 3rd: Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4(+) T cells against the swine-origin H1N1 influenza virus. Vaccine 2011, 29(17):3299-3309.
  • [13]Ge X, Tan V, Bollyky PL, Standifer NE, James EA, Kwok WW: Assessment of seasonal influenza A virus-specific CD4 T-cell responses to 2009 pandemic H1N1 swine-origin influenza A virus. J Virol 2010, 84(7):3312-3319.
  • [14]Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L, et al.: Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol 2010, 84(13):6527-6535.
  • [15]NCBI FASTA. http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/nph-select.cgi?go=alignment webcite
  • [16]Falfan-Valencia R, Camarena A, Juarez A, Becerril C, Montano M, Cisneros J, Mendoza F, Granados J, Pardo A, Selman M: Major histocompatibility complex and alveolar epithelial apoptosis in idiopathic pulmonary fibrosis. Hum Genet 2005, 118(2):235-244.
  • [17]Singh H, Raghava GP: ProPred: prediction of HLA-DR binding sites. Bioinformatics 2001, 17(12):1236-1237.
  • [18]WHO: Manual for the laboratory diagnosis and virological surveillance of influenza. Geneva, Switzerland: WHO Press; 2002:153.
  • [19]Guideline on influenza vaccines prepared from viruses with the potential to cause a pandemic and intended for use outside of the core dossier context In Committee for Human Medicinal Products, Doc Ref. EMEA/CHMP/VWP/263499/2006. London, United Kingdon: European Medicines Agency; 2007.
  • [20]Schwander SK, Torres M, Sada E, Carranza C, Ramos E, Tary-Lehmann M, Wallis RS, Sierra J, Rich EA: Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar lymphocytes during active pulmonary tuberculosis. J Infect Dis 1998, 178(5):1434-1445.
  • [21]Duvvuri VR, Duvvuri B, Jamnik V, Gubbay JB, Wu J, Wu GE: T cell memory to evolutionarily conserved and shared hemagglutinin epitopes of H1N1 viruses: a pilot scale study. BMC Infect Dis 2013, 13:204. BioMed Central Full Text
  • [22]Randles RH: WD: Introduction to the Theory of Nonparametric Statistics. New York: John Wiley & Sons; 1979.
  • [23]Wagar LE, Rosella L, Crowcroft N, Lowcock B, Drohomyrecky PC, Foisy J, Gubbay J, Rebbapragada A, Winter AL, Achonu C, et al.: Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian cohort one year post-pandemic: implications for vaccination. PloS one 2011, 6(11):e28063.
  • [24]Lagler H, Grabmeier-Pfistershammer K, Touzeau-Romer V, Tobudic S, Ramharter M, Wenisch J, Gualdoni GA, Redlberger-Fritz M, Popow-Kraupp T, Rieger A, et al.: Immunogenicity and Tolerability after Two Doses of Non-Adjuvanted, Whole-Virion Pandemic Influenza A (H1N1) Vaccine in HIV-Infected Individuals. PloS one 2012, 7(5):e36773.
  • [25]Li GM, Chiu C, Wrammert J, McCausland M, Andrews SF, Zheng NY, Lee JH, Huang M, Qu X, Edupuganti S, et al.: Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A 2012, 109(23):9047-9052.
  • [26]Choi YS, Baek YH, Kang W, Nam SJ, Lee J, You S, Chang DY, Youn JC, Choi YK, Shin EC: Reduced antibody responses to the pandemic (H1N1) 2009 vaccine after recent seasonal influenza vaccination. Clin Vaccine Immunol 2011, 18(9):1519-1523.
  • [27]Air GM, Feng J, Chen T, Joachims ML, James JA, Thompson LF: Individual antibody and T cell responses to vaccination and infection with the 2009 pandemic swine-origin H1N1 influenza virus. J Clin Immunol 2011, 31(5):900-912.
  • [28]Iorio AM, Bistoni O, Galdiero M, Lepri E, Camilloni B, Russano AM, Neri M, Basileo M, Spinozzi F: Influenza viruses and cross-reactivity in healthy adults: humoral and cellular immunity induced by seasonal 2007/2008 influenza vaccination against vaccine antigens and 2009 A(H1N1) pandemic influenza virus. Vaccine 2012, 30(9):1617-1623.
  • [29]Greenbaum JA, Kotturi MF, Kim Y, Oseroff C, Vaughan K, Salimi N, Vita R, Ponomarenko J, Scheuermann RH, Sette A, et al.: Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population. Proc Natl Acad Sci U S A 2009, 106(48):20365-20370.
  • [30]Mahnke YD, Saqr A, Hazenfeld S, Brady RC, Roederer M, Subbramanian RA: Age-related changes in durability and function of vaccine-elicited influenza-specific CD4(+) T-cell responses. Vaccine 2011, 29(47):8606-8614.
  • [31]Scheible K, Zhang G, Baer J, Azadniv M, Lambert K, Pryhuber G, Treanor JJ, Topham DJ: CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses. Vaccine 2011, 29(11):2159-2168.
  • [32]Roman F, Clement F, Dewe W, Walravens K, Maes C, Willekens J, De Boever F, Hanon E, Leroux-Roels G: Effect on cellular and humoral immune responses of the AS03 adjuvant system in an A/H1N1/2009 influenza virus vaccine administered to adults during two randomized controlled trials. Clin Vaccine Immunol 2011, 18(5):835-843.
  • [33]Stephenson I, Hayden F, Osterhaus A, Howard W, Pervikov Y, Palkonyay L, Kieny MP: Report of the fourth meeting on ‘Influenza vaccines that induce broad spectrum and long-lasting immune responses’, World Health Organization and Wellcome Trust, London, United Kingdom, 9–10 November 2009. Vaccine 2010, 28(23):3875-3882.
  • [34]Strutt TM, McKinstry KK, Dibble JP, Winchell C, Kuang Y, Curtis JD, Huston G, Dutton RW, Swain SL: Memory CD4+ T cells induce innate responses independently of pathogen. Nat Med 2010, 16(5):558-564. 551p following 564
  • [35]Boon AC, de Mutsert G, van Baarle D, Smith DJ, Lapedes AS, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF: Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes. J Immunol 2004, 172(4):2453-2460.
  文献评价指标  
  下载次数:57次 浏览次数:24次