Short Communications
The effects of Bifidobacterium animalis subsp. lactis and vitamin D on immunological response following vaccination in puppies
Gökhan Saridag ,
Songul Erdogan ,
Tahir Ozalp ,
Kerem Ural ,
Hasan Erdogan *

Mac Vet Rev 2023; 46 (2): i - viii


Received: 27 March 2023

Received in revised form: 01 July 2023

Accepted: 09 August 2023

Available Online First: 15 September 2023

Published on: 15 October 2023

Correspondence: Hasan Erdogan,


This study aimed to determine the effects of oral application of Bifidobacterium animalis subsp. lactis and vitamin D on the immune response after vaccination in puppies. Crossbred dogs at the age of 55–65 days (n=21) of both sexes were grouped according to the application as follows: Group 1 - commercial polyvalent vaccine only (Vanguard 5L4, Zoetis); Group 2 - polyvalent vaccine and vitamin D; and Group 3 - polyvalent vaccine, B. animalis subsp. lactis, and vitamin D. The antibody titers, measured 3 weeks after the vaccination and after the 1st booster, demonstrated sufficient protective levels against the canine distemper virus but without significant difference between the groups when compare both values. No significant differences either, were observed in antibody titers against canine parvovirus after the initial vaccination. However, after the 1st booster, Group 2 samples showed significantly higher antibody titer value compared to the other groups (p<0.05). In conclusion, the dogs included in this study had an adequate antibody response to canine parvovirus and distemper viruses following the vaccination and 1st booster in all three groups of animals, and significant increasing of protective antibody titers against canine parvovirus virus the after the 1st booster in the group where B. animalis subsp. lactis was included.

Keywords: antibody response, Bifidobacterium animalis subsp. lactis, canine parvovirus, vaccination, vitamin D


1. Belsare, A.V., Vanak, A.T., Gompper, M.E. (2014). Epidemiology of viral pathogens of free‐ranging dogs and Indian foxes in a human‐dominated landscape in central India. Transbound Emerg Dis. 61(Suppl. 1): 78-86. PMid:25135467
2. Greene, G.E., Appel, M.J. (1990). Infectious diseases of the dog and cat. In: C.R. Greene (Ed.), Saunder Philadelphia, Pennsylvania, 226-241.
3. Appel, M.J., Cooper, B.J., Greisen, H.E.L.E.N., Scott, F., Carmichael, L.E. (1979). Canine viral enteritis. I. Status report on corona-and parvo-like viral enteritides. Cornell Vet. 69(3): 123-133.
4. Prittie, J. (2004). Canine parvoviral enteritis: a review of diagnosis, management, and prevention. J Vet Emerg Crit Care. 14(3): 167-176. 
5. Kim, D.Y., Zinn, M.M., Odemuyiwa, S.O., Mitchell Jr, W.J., Johnson, G.C. (2021). Myocarditis caused by naturally acquired canine distemper virus infection in 4 dogs. J Vet Diagn Invest. 33(1): 167-169. PMid:33164720 PMCid:PMC7758698
6. Nova, B.V., Cunha, E., Sepúlveda, N., Oliveira, M., São Braz, B., Tavares, L., Almeida, V., Gil, S. (2018). Evaluation of the humoral immune response induced by vaccination for canine distemper and parvovirus: a pilot study. BMC Vet Res. 14, 348. PMid:30445957 PMCid:PMC6240190
7. Carmichael, L.E., Joubert, J.C., Pollock, R.V. (1980). Hemagglutination by canine parvovirus: serologic studies and diagnostic applications. Am J Vet Res. 41(5): 784-791.
8. Appel, M.J.G. (1999). Forty years of canine vaccination. Adv Vet Med. 41, 309-324. PMid:9890024
9. Decaro, N., Buonavoglia, C., Barrs, V.R. (2020). Canine parvovirus vaccination and immunisation failures: Are we far from disease eradication? Vet Microbiol. 108760. PMid:32768213 PMCid:PMC7295477
10. Szymczak, I., Pawliczak, R. (2016). The active metabolite of vitamin D3 as a potential immunomodulator. Scand J Immunol. 83(2): 83-91. PMid:26678915
11. Fitch, N., Becker, A.B., HayGlass, K.T. (2016). Vitamin D [1, 25 (OH)2D3] differentially regulates human innate cytokine responses to bacterial versus viral pattern recognition receptor stimuli. J Immunol. 196(7): 2965-2972. PMid:26895836
12. Ooi, J.H., McDaniel, K.L., Weaver, V., Cantorna, M.T. (2014). Murine CD8+ T cells but not macrophages express the vitamin D 1α-hydroxylase. J Nutr Biochem. 25(1): 58-65. PMid:24314866 PMCid:PMC3857601
13. Matheu, V., Bäck, O., Mondoc, E., Issazadeh-Navikas, S. (2003). Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease. J Allergy Clin Immunol. 112(3): 585-592. PMid:13679819
14. Maalmi, H., Berraïes, A., Tangour, E., Ammar, J., Abid, H., Hamzaoui, K., Hamzaoui, A. (2012). The impact of vitamin D deficiency on immune T cells in asthmatic children: a case-control study. J Asthma Allergy. 5, 11-19. PMid:22690128 PMCid:PMC3363015
15. Goncalves-Mendes, N., Talvas, J., Dualé, C., Guttmann, A., Corbin, V., Marceau, G., et al. (2019). Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial. Front Immunol. 10, 65. PMid:30800121 PMCid:PMC6375825
16. Patel, N., Penkert, R.R., Jones, B.G., Sealy, R.E., Surman, S.L., Sun, Y., et al. (2019). Baseline serum vitamin A and D levels determine benefit of oral vitamin A&D supplements to humoral immune responses following pediatric influenza vaccination. Viruses 11(10): 907. PMid:31575021 PMCid:PMC6832482
17. Bottacini, F., van Sinderen, D., Ventura, M. (2017). Omics of bifidobacteria: research and insights into their health -promoting activities. Biochem J. 474(24): 4137-4152. PMid:29212851
18. Hidalgo-Cantabrana, C., Delgado, S., Ruiz, L., Ruas-Madiedo, P., Sánchez, B., Margolles, A. (2017). Bifidobacteria and their health‐ promoting effects. Microbiol Spectr. 5(3). PMid:28643627
19. Thomas, C.M., Versalovic, J. (2010). Probiotics-host communication: modulation of signaling pathways in the intestine. Gut Microbes 1(3): 148-163. PMid:20672012 PMCid:PMC2909492
20. Pang, I.K., Iwasaki, A. (2011). Inflammasomes as mediators of immunity against influenza virus. Trends Immunol. 32(1): 34-41. PMid:21147034 PMCid:PMC3017631
21. Zimmermann, P., Curtis, N. (2018). The influence of probiotics on vaccine responses-A systematic review. Vaccine 36(2): 207-213. PMid:28923425
22. Huda, M.N., Lewis, Z., Kalanetra, K.M., Rashid, M., Ahmad, S.M., Raqib, R., et al. (2014). Stool microbiota and vaccine responses of infants. Pediatrics 134(2): e362-e372. PMid:25002669 PMCid:PMC4187229
23. Rizzardini, G., Eskesen, D., Calder, P.C., Capetti, A., Jespersen, L., Clerici, M. (2012). Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr. 107(6): 876-884. PMid:21899798
24. Grubczak, K., Lipinska, D., Eljaszewicz, A., Singh, P., Radzikowska, U., Miklasz, P., et al. (2015). Vitamin D3 treatment decreases frequencies of CD16-positive and TNF-α-secreting monocytes in asthmatic patients. Int Arch Allergy Immunol. 166(3): 170-176. PMid:25872112
25. Neve, A., Corrado, A., Cantatore, F.P. (2014). Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis. Clin Exp Med. 14(3): 275-283. PMid:23824148
26. Aranow, C. (2011). Vitamin D and the immune system. J Investig Med. 59(6): 881-886. PMid:21527855 PMCid:PMC3166406
27. Milani, C., Mangifesta, M., Mancabelli, L., Lugli, G.A., James, K., Duranti, S., et al. (2017). Unveiling bifidobacterial biogeography across the mammalian branch of the tree of life. ISME J. 11, 2834-2847. PMid:28837128 PMCid:PMC5702741
28. Ventura, M., Turroni, F., Motherway, M.O., MacSharry, J., van Sinderen, D. (2012). Host-microbe interactions that facilitate gut colonization by commensal bifidobacteria. Trends Microbiol. 20(10): 467-476. PMid:22902802
29. Mahooti, M., Abdolalipour, E., Salehzadeh, A., Mohebbi, S.R., Gorji, A., Ghaemi, A. (2019). Immunomodulatory and prophylactic effects of Bifidobacterium bifidum probiotic strain on influenza infection in mice. World J Microbiol Biotechnol. 35(6): 91. PMid:31161259
30. Oh, J.Z., Ravindran, R., Chassaing, B., Carvalho, F.A., Maddur, M.S., Bower, M., et al. (2014). TLR5- mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41(3): 478-492. PMid:25220212 PMCid:PMC4169736
31. Grönlund, M.M., Arvilommi, H., Kero, P., Lehtonen, O.P., Isolauri, E. (2000). Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months. Arch Dis Child Fetal Neonatal Ed. 83(3): F186-F192. PMid:11040166 PMCid:PMC1721174
32. Lundell, A.C., Björnsson, V., Ljung, A., Ceder, M., Johansen, S., Lindhagen, G., Rudin, A. (2012). Infant B cell memory differentiation and early gut bacterial colonization. J Immunol. 188(9): 4315-4322. PMid:22490441
33. Sjögren, Y.M., Tomicic, S., Lundberg, A., Böttcher, M.F., Björkstén, B., Sverremark‐Ekström, E., Jenmalm, M.C. (2009). Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses: gut microbiota and immune responses. Clin Exp Allergy. 39(12): 1842-1851. PMid:29252042 PMCid:PMC8826512
34. Velasquez, D.E., Parashar, U., Jiang, B. (2018). Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors. Expert Rev Vaccines.17(2): 145-161. PMid:29252042 PMCid:PMC8826512
35. Perdrizet, J.A., Shiau, D.S., Xie, H. (2019). The serological response in dogs inoculated with canine distemper virus vaccine at the acupuncture point governing vessel-14: A randomized controlled trial. Vaccine 37(13): 1889-1896. PMid:30799157


© 2023 Ergodan H. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conflict of Interest Statement

The authors declared that they have no potential lict of interest with respect to the authorship and/or publication of this article.

Citation Information

Macedonian Veterinary Review. Volume 46, Issue 2, Pages i-viii, e-ISSN 1857-7415, p-ISSN 1409-7621, DOI: 10.2478/macvetrev-2023-0025