A Comparative Study of the Effects of Al(OH)3 and AlPO4 Adjuvants on the Production of Neutralizing Antibodies (NAbs) against Bovine parainfluenza Virus Type 3 (BPIV3) in Guinea Pigs

Document Type : Original Articles

Authors

1 Department of Microbiology and immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

3 Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

10.32592/ARI.2023.78.6.1779

Abstract

Aluminum-containing adjuvants are extensively used for inactive human and animal vaccines owing to their favorable immunostimulative and safe properties. Nonetheless, there is controversy over the effects of different aluminum salts as an adjuvant for the bovine parainfluenza virus type 3 (BPIV3) vaccine. In order to find a suitable adjuvant, we studied the effects of two adjuvants (i.e., aluminum hydroxide [Al(OH)3] and aluminum potassium sulfate [AlPO4]) on the production of neutralizing antibodies (NAbs) for an experimental BPIV3 vaccine. The animals under study (Guinea pigs) were randomly assigned to five groups of experimental vaccines containing Al(OH)3 (AH), AlPO4 (AP), Al(OH)3-AlPO4 mixture (MIX), commercial vaccine (COM), and control (NS). The treatment groups were immunized with two doses of vaccine 21 days apart (on days 0 and 21), and the control group received normal saline under the same conditions. The animals were monitored for 42 days, and blood samples were then taken. The results indicated that all vaccines were able to induce the production of NAbs at levels higher than the minimum protective titer (0.6). An increase in titer was observed throughout the monitoring period. Moreover, an increase in both the level and mean titer of NAbs obtained from the vaccine containing Al(OH)3 adjuvant was significantly higher than in the other studied groups (P≤0.005). The comparison of NAbs titer in other groups did not display a significant difference. Considering the speed of rising and the optimal titer of NAbs production in the experimental vaccine, the Al(OH)3 adjuvant is a suitable candidate for preparing a vaccine against BPIV3 for immunization.

Keywords

Main Subjects


References
1. Cao Y, Zhu X, Hossen MN, Kakar P, Zhao Y, Chen X.
Augmentation of vaccine-induced humoral and cellular
immunity by a physical radiofrequency adjuvant. Nature
communications. 2018;9(1):1-13.
2. Aguilar J, Rodriguez E. Vaccine adjuvants revisited.
Vaccine. 2007;25(19):3752-62.
3. Shah RR, Hassett KJ, Brito LA. Overview of vaccine
adjuvants: Introduction, history, and current status.
Vaccine Adjuvants. 2017:1-13.
4. Apostolico JdS, Lunardelli VAS, Coirada FC,
Boscardin SB, Rosa DS. Adjuvants: classification,
modus operandi, and licensing. Journal of immunology
research. 2016;2016.
5. Cohen S, Shafferman A. Novel Strategies in the Design
and Production of Vaccines: Springer Science &
Business Media; 1996.
6. HogenEsch H, O’Hagan DT, Fox CB. Optimizing the
utilization of aluminum adjuvants in vaccines: you
might just get what you want. npj Vaccines.
2018;3(1):1-11.
7. Facciolà A, Visalli G, Laganà A, Di Pietro A. An
Overview of Vaccine Adjuvants: Current Evidence and
Future Perspectives. Vaccines. 2022;10(5.819:)
8. Ghimire TR. The mechanisms of action of vaccines
containing aluminum adjuvants: an in vitro vs in vivo
paradigm. Springerplus. 2015;4(1):1-18.
9. Lu F, HogenEsch H. Kinetics of the inflammatory
response following intramuscular injection of aluminum
adjuvant. Vaccine. 2013;31(37):3979-86.
10. He P, Zou Y, Hu Z. Advances in aluminum hydroxidebased adjuvant research and its mechanism. Human
vaccines & immunotherapeutics. 2015;11(2):477-88.
11. Leroux-Roels G. Unmet needs in modern vaccinology:
adjuvants to improve the immune response. Vaccine.
2010;28:C25-C36.
12. Leslie M. Solution to vaccine mystery starts to
crystallize. American Association for the Advancement
of Science; 2013.
13. Ghimire TR, Benson RA, Garside P, Brewer JM. Alum
increases antigen uptake, reduces antigen degradation
and sustains antigen presentation by DCs in vitro.
Immunology letters. 2012;147(1-2):55-62.
14. Güven E, Duus K, Laursen I, Højrup P, Houen G.
Aluminum hydroxide adjuvant differentially activates
the three complement pathways with major involvement
of the alternative pathway. PLoS One. 2013;
8(9):e74445.
15. Zandieh S, Lotfi M, Kamalzadeh M, Shiri N, Parmour
E, Eshaghi A, et al. The Characteristics of an Ovine
Lymphoid Cell-Line sensitive to Vaccinal Infectious
Bursal Disease Virus Strain. Archives of Razi Institute.
2017;72(3):173-9.
16. Supply V, Organization WH. Manual of laboratory
methods for testing of vaccines used in the WHO
Expanded Programme on Immunization. World Health
Organization; 1997.
17. Sobhani M, Lotfi M, Saifi Shapouri MR. Investigating
the sensitivity of CEF, BT, MDBK and Vero cell lines
compared to RBK cell to the replication of bovine
parainfluenza virus type 3 (bPI3V). Veterinary research
and biological products. 2018;31(1):48-57. [in persion]
18. Argento E, Barros V, Gleser H, Ióppolo M, Mórtola E,
Parreño V, et al. Potencia y eficacia para vacunas
bovinas que contengan en su formulación herpesvirus
bovino 1 (Bohv-1) agente causal de la.
19.I EL-Hawary R, A Mostafa H. Immunological response
of locally prepared oil adjuvanted pneumo 5-vaccine in
calves. Journal of Veterinary Medical Research.
2017;24(1):41-7.
20. Egli A, Santer DM, O'Shea D, Barakat K, Syedbasha M,
Vollmer M, et al. IL-28B is a key regulator of B-and Tcell vaccine responses against influenza. PLoS
pathogens. 2014;1:)12(0e1004556.
21. Zaccaro DJ, Wagener DK, Whisnant CC, Staats HF.
Evaluation of vaccine-induced antibody responses:
impact of new technologies. Vaccine. 2013;
31(25):2756-61.
22. Park M-E, Lee S-Y, Kim R-H, Ko M-K, Lee K-N, Kim
S-M, et al. Enhanced immune responses of foot-andmouth disease vaccine using new oil/gel adjuvant
mixtures in pigs and goats. Vaccine. 2014;32(40):5221-7.
23.Rosado-Vallado M, Mut-Martin M, del Rosario GarcíaMiss M, Dumonteil E. Aluminium phosphate
potentiates the efficacy of DNA vaccines against
Leishmania mexicana. Vaccine. 2005;23(46-47):5372-9.
24.Issa AM, Salim MS, Zidan H, Mohamed AF, Farrag ARH. Evaluation of the effects of aluminum phosphate
1786 Heidary et al / Archives of Razi Institute, Vol. 78, No. 6 (2023) 1779-1786
and calcium phosphate nanoparticles as adjuvants in
vaccinated mice. International Journal of Chemical
Engineering and Applications. 2014;5(5):367.
25. Mahboubi A, Fazeli MR, Dinavand R, Samadi N,
Sharifzadeh M, Ilka H, et al. Comparison of the
Adjuvanticity of Aluminum Salts and Their
Combination in Hepatitis B Recombinant Protein
Vaccine Assessed in Mice. Iranian Journal of
Immunology. 2008;5(3):163-70.
26. Liang Z, Ren H, Lang Y, Li Y. Enhancement of a
hepatitis B DNA vaccine potency using aluminum
phosphate in mice. Zhonghua gan Zang Bing za zhi=
Zhonghua Ganzangbing Zazhi= Chinese Journal of
Hepatology. 2004;12(2):79-81.
27. Akbarian M, Keyvanfar H, Lotfi M. Preparation of an
Inactivated Peste des Petits Ruminants Vaccine and Its
Comparative Immunogenicity Evaluation in an Animal
Model. Archives of Razi Institute. 2021;76(4)731.
28. Kooijman S, Vrieling H, Verhagen L, de Ridder J, de
Haan A, van Riet E, et al. Aluminum Hydroxide And
Aluminum Phosphate Adjuvants Elicit A Different
Innate Immune Response. Journal of Pharmaceutical
Sciences. 2022;111(4):982-90.
29. Mei C, Deshmukh S, Cronin J, Cong S, Chapman D,
Lazaris N, et al. Aluminum phosphate vaccine adjuvant:
analysis of composition and size using off-line and inline tools. Computational and structural biotechnology
journal. 2019;17:1184-94.
30.World Organization for Animal Health, Manual of
Diagnostic Tests and Vaccines for Terrestrial Animals.
Foot And Mouth Disease (Infection With Foot And
Mouth Disease Virus) 2022 . Chapter 3.1.8 . p: 1-3