APPLICATION OF METHOD BASED ON IN VITRO ANTIBODY QUANTIFICATION IN PBMC SUPERNATANT SAMPLES FOR IMMUNOGENICITY EVALUATION OF A (H5N1) AND A (H5N2) POTENTIALLY PANDEMIC INFLUENZA VACCINES IN CLINICAL TRIALS
https://doi.org/10.15789/1563-0625-2016-2-129-138
Abstract
There are many data worldwide which suggest that the methods for evaluation of influenza vaccines immunogenicity should be improved. The only method validated in Russia is a HAI (haemagglutination inhibition) assay with serum samples from vaccinated volunteers. This assay does not, however, completely reflect the vaccine-induced immunological changes. In this study, we evaluated antibody immune responses to A (H5N1) inactivated influenza vaccine boosting in healthy volunteers previously primed with A (H5N2) live attenuated influenza vaccine. We compared three methods of antibody detection: (i) HAI assay with serum samples; (ii) ELISA with serum samples; (iii) ELISA with PBMC (peripheral blood mononuclear cells) culture supernates, i.e., an alternative test based on quantification of antibodies secreted by PBMC in vitro. The latter test was shown to have an advantage over other techniques in IgA and IgG antibody detection at early timepoints (day 7) after vaccination. The first two methods allowed immunogenicity assessment at day 28 after vaccination.
Thus, a test based on antibody quantification in PBMC supernatant samples can be used as an alternative method for evaluation of influenza vaccines immunogenicity. This method also exhibits a better strainspecificity.
About the Authors
I. V. Losev
Research Institute of Experimental Medicine
Russian Federation
Russian Federation
Research Associate, Laboratory of Immunology and Prophylaxis of Viral Infections, Departament of Virology,
197376, St. Petersburg, Acad. Pavlov str., 12
S. A. Donina
Research Institute of Experimental Medicine
Russian Federation
Russian Federation
PhD (Medicine), Laboratory of Immunology and Prophylaxis of Viral Infections, Departament of Virology,
St. Petersburg
G. D. Petukhova
Research Institute of Experimental Medicine
Russian Federation
Russian Federation
PhD (Biology), Senior Research Associate, Laboratory of Immunology and Prophylaxis of Viral Infections, Department of Virology,
St. Petersburg
M. K. Erofeeva
Research Institute of Influenza
Russian Federation
Russian Federation
PhD, MD (Medicine), Head, Laboratory for Trials of Novel Antiviral Remedies,
St. Petersburg
L. G. Rudenko
Research Institute of Experimental Medicine
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Head, Department of Virology,
St. Petersburg
A. N. Naykhin
Research Institute of Experimental Medicine
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Head, Laboratory of Immunology and Prophylaxis of Viral Infections, Department of Virology,
St. Petersburg
References
1. Донина С.А., Петухова Г.Д., Кореньков Д.А., Григорьева Е.П., Кузнецова С.А., Лосев И.В., Руденко Л.Г., Найхин А.Н. Локальный и гуморальный иммунный ответ у больных гриппом и у лиц, привитых против сезонных и пандемических вирусов гриппа А // Вопросы вирусологии, 2013. Т. 58, № 3. С. 37-42. [Donina S.A., Petukhova G.D., Korenkov D.A., Grigorieva E.P., Kuznetsova S.A., Losev I.V., Rudenko L.G., Naykhin A.N. Local Antibody Immune Responses in Influenza Patients and Persons Vaccinated with Seasonal, Pre-pandemic, and Pandemic Live Attenuated Influenza Vaccines. Voprosy virusologii = Problems of Virology, 2013, Vol. 58, no. 3, pp. 37-42. (In Russ.)]
2. Найхин А.Н., Артемьева С.А., Выборных Е.Н., Попова Т.Л., Каторгина Л.Г., Ким Т.Н., Кустикова Ю.Г., Денисов Г.М. Роль функциональной активности антител в защищенности людей от гриппа // Вопросы вирусологиия, 1991. Т. 36, № 3. С. 194-197. [Naikhin A.N., Artemyeva S.A., Vybornykh E.N., Popova T.L., Katorgina L.G., Kim T.N., Kustikova Yu.G., Denisov G.M. The role of antibody functional activity in the protection of people against influenza. Voprosy virusologii = Problems of Virology, 1991, Vol. 36, no. 3, pp. 194-197. (In Russ.)]
3. Найхин А.Н. Гетеросубтипический иммунитет к вирусам гриппа А: эпидемиологические данные, вовлеченность разных иммунологических факторов, вакцинация // Вопросы вирусологии, 2012. Т. 57, № 3. С. 4-9. [Naikhin A.N. Heterosubtypic immunity to influenza A viruses: epidemiological data, involvement of different immunological factors, vaccination. Voprosy virusologii = Problems of Virology, 2012, Vol. 57, no. 3, pp. 4-9. (In Russ.)]
4. Ярилин А.А. Иммунология: учебник. М.: Гэотар Медиа, 2010. 749 с. [Yarilin A.A. Immunology]. Moscow: GEOTAR-Media, 2010. 749 p.
5. Benner R., Hijmans W., Haaijman J.J. The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation. Clin. Exp. Immunol., 1981, Vol. 46, no. 1, pp. 1-8.
6. Cox R.J., Brokstad K.A., Zuckerman M.A., Wood J.M., Haaheim L.R., Oxford J.S. An early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination. Vaccine, 1994, Vol. 12, no. 11, pp. 993-999.
7. Ershler W.B., Moore A.L., Hacker M.P. Specific in vivo and in vitro antibody response to tetanus toxoid immunization. Clin. Exp. Immunol., 1982, Vol. 49, no. 3, pp. 552-558.
8. Ershler W.B., Coe C.L., Gravenstein S., Schultz K.T., Klopp R.G. Specific antibody synthesis in vitro. IV. The correlation of in vitro and in vivo antibody response to influenza vaccine in rhesus monkeys. Clin. Exp. Immunol., 1988, Vol. 73, no. 3, pp. 355-3659.
9. He X.S., Sasaki S., Narvaez C.F. Plasmablast-derived polyclonal antibody response after influenza vaccination. Journal of Immunological Methods, 2011, Vol. 365, pp. 67-75.
10. Kunkel E.J., Butcher E.C.. Chemokines and the tissue-specific migration of lymphocytes. Immunity, 2002, Vol. 16, no. 1, pp. 1-4.
11. Kunkel E.J., Butcher E.C. Plasma-cell homing. Nat. Rev. Immunol., 2003, Vol. 3, no. 10, pp. 822-829.
12. Rowe T., Abernathy R.A., Hu-Primmer J. Detection of antibody to avian influenza A(H5N1) virus in human serum by using a combination of serologic assay. J. Clin. Microbiol., 1999, Vol. 37, pp. 937-943.
13. Rudenko L., Naykhin A., Donina S. Assessment of immune responses to H5N1 inactivated influenza vaccine among individuals previously primed with H5N2 live attenuated influenza vaccine. Human Vaccines and Immunotherapeutics, 2015 [in print].
14. Qadri F., Ryan E.T., Faruque A.S., Ahmed F., Khan A.I., Islam M.M., Akramuzzaman S.M., Sack D.A., Calderwood S.B. Antigen-specific immunoglobulin A antibodies secreted from circulating B cells are an effective marker for recent local immune responses in patients with cholera: comparison to antibody-secreting cell responses and other immunological markers. Infect. Immun., 2003, Vol. 71, no. 8, pp. 4808-4814.
15. Sheikh A., Bhuiyan M.S., Khanam F., Chowdhury F., Saha A., Ahmed D., Jamil K.M., LaRocque R.C., Harris J.B., Ahmad M.M., Charles R., Brooks W.A., Calderwood S.B., Cravioto A., Ryan E.T., Qadri F. Salmonella enterica serovar Typhi-specific immunoglobulin A antibody responses in plasma and antibody in lymphocyte supernatant specimens in Bangladeshi patients with suspected typhoid fever. Clin. Vaccine Immunol., 2009, Vol. 16, no. 11, 1587-1594.
16. Treanor J., Wright P.F. Immune correlates of protection against influenza in the human challenge model. Dev. Biol. (Basel), 2003, Vol. 115, pp. 97-104.
Review
For citations:
Losev I.V., Donina S.A., Petukhova G.D., Erofeeva M.K., Rudenko L.G., Naykhin A.N. APPLICATION OF METHOD BASED ON IN VITRO ANTIBODY QUANTIFICATION IN PBMC SUPERNATANT SAMPLES FOR IMMUNOGENICITY EVALUATION OF A (H5N1) AND A (H5N2) POTENTIALLY PANDEMIC INFLUENZA VACCINES IN CLINICAL TRIALS. Medical Immunology (Russia). 2016;18(2):129-138. (In Russ.) https://doi.org/10.15789/1563-0625-2016-2-129-138
Views:
1146
Email this article 