Influence of the Host Factors on Human Papillomavirus Infection and Vaccine Efficacy

Sung-Hwa Sohn; Jae-Hwan Nam

doi:10.4167/jbv.2015.45.3.179

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Sohn and Nam: Influence of the Host Factors on Human Papillomavirus Infection and Vaccine Efficacy

Review Article

J Bacteriol Virol 2015;45(3):179-188.

Published online: 9 February 2015

DOI: https://doi.org/10.4167/jbv.2015.45.3.179

Influence of the Host Factors on Human Papillomavirus Infection and Vaccine Efficacy

Sung-Hwa Sohn, Jae-Hwan Nam^∗

Department of Biotechnology, The Catholic University of Korea, Gyeonggi-do, Korea

^∗Corresponding author: Jae-Hwan Nam, Ph.D. Department of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon, Gyeonggi-do, 420-743, Korea. Phone: +82-2-2164-4852, Fax: +82-2-2164-4917, e-mail: jhnam@catholic.ac.kr

^∗∗ This study was supported by a grant from the Korean Healthcare Technology R&D project of the Ministry of Health & Welfare (A103001 and HI13C0826), and by a grant from Gyunggi Regional Research Center (GRRC) of the Catholic University of Korea.

Received 30 May 201510 June 2015 Accepted 25 June 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human papillomavirus (HPV) is associated with cervical cell changes, genital warts, recurrent respiratory papillomatosis, laryngeal papillomatosis, head and neck cancer, and cervical cancer. Two commercial HPV vaccines have successfully been made available in the clinical field. This review covers the progress of cervical disease by understanding the nature of HPV infection, as well as the relationship between the host factors and HPV vaccine effectiveness. Among these host factors, microbiota has been revealed to influence the development and function of both the innate and adaptive immune systems. Therefore, the composition of the microbiome may ultimately affect vaccine efficacy. Understating the relationship between host factors and HPV infection/vaccine efficacy may prove to be useful in earlier diagnosis, as well as disease prophylaxis.

Keywords: HPV, Vaccine efficacy, Probiotics, Microbiota

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Figure 1.

A schematic diagram of a possible mode of the oncogenic action of human papillomavirus (HPV). HPV infection into a host tissue leads to oncogenic processes. HPV E5 protein suppresses the expression of MHC class I and antigen processing. HPV E6 protein binds p53 tumor suppressor protein and this binding blocks p53 defense mechanisms, as well as p53-induced antiviral activity (down-regulates the expression of the antiviral interferon-related genes and the transcription factor NF-κB), through cell cycle arrest and apoptosis of the infected cell by degradation of p53 via ubiquitination. HPV E7 protein binds pRb cell cycle regulatory protein, which can block cell cycle arrest by degradation of Rb via ubiquitination. Therefore, these proteins play roles in tumor promotion. These HPV E5, E6, and E7 proteins are able to impair the innate and acquired immune response, which play roles in the evasion of the host immune system. MHC class I, major histcompatibility complex class I; pRb, retinoblastoma protein; Ag, antigen; IFN, interferon gamma; NF-κB, nuclear factor-κB.

Figure 2.

A schematic diagram of possible mode for the relationship between the microbiota and the immune system in the intestinal lamina propria. The microbiota is composed of a variety of bacteria with different characters. The microbiota influence the development and function of both the innate and adaptive immune systems. The intestinal microflora has TLR5 ligans such as flagellin. TLR5 signaling stimulates CD11b^high CD11c^high DCs, which can catalyze the conversion of vitamin A to retinoic acid; this causes B cells to differentiate into IgA producing plasma cells. Secreted IgA regulates the ecological balance of microbiota, which regulates the composition and character of microbiota. Ultimately, IgA induces compartmentalization of the microbiota to the intestinal lumen, and it contributes to protection from viral infections. HPV, human papillomavirus; TLR5, toll like receptor 5; DC, dendritic cell; IgA, immunoglobulin A; Raldh2, retinaldehyde dehydrogenase 2.

Table 1.

Characteristics of anti-HPV vaccines

	Bivalent vaccine	Quadrivalent vaccine	Ninevalent vaccine
Commercial name	Cervarix^®	Gardasil^®	Gardasil^® 9
HPV types	HPV 16/ 18	HPV 6/ 11/ 16/ 18	HPV 6/ 11/ 16/ 18/ 31/ 33/ 45/ 52/ 58
Producer cells	Trichoplusia ni (Hi 5) insect cell line infected with L1 recombinant baculovirus	Saccharomyces cerevisiae expressing L1	Saccharomyces cerevisiae expressing L1
Administration schedule	Girls and women: 9~14 years: 0, 1, 6 months	Girls and women: 9~13 years: 0, 2, 6 months	Girls and women: 9~26 years: 0, 2, 6 months Boys: 9~15 years: 0, 2, 6 months
Adjuvant	Aluminum hydroxyphosphate sulfate	Aluminum hydroxide and 3-O-deacylated-4-monophosphoryl lipid A	Aluminum hydroxyphosphate sulfate or AAHS

Table 2.

Summary of the impact of probiotics on vaccine efficacy

Probiotics	Vaccines	Biological effects
Lacrobacillus casei strain GG (LGG)	D x RRV rhesus-human reassortant rotavirus vaccine	LGG has an immunostimulatinq effect on rotavirus vaccination via enhance IgA production and release of interferon γ.
LGG or Lactococcus lactis (L. lactis)	Salmonella typhi Ty21a vaccine	LGG stimulated IgA sASC responses against S. typhi Ty21a. L. lactis has increase CR3 receptor expression on the neutrophils which can influence the non-specific immune response.
LGG and Bifidobacterium lactis BB12 (BB12)	AttHRV vaccine	LGG and BB12 acted as an immunostimulant for AttHRV vaccine via modulated DC activation and responses.
L. lactis, Lactobacillus plantarum or Bifidobacterium bifidum	Allergy vaccines	These bacteria have induction of Th1 response in eczema and asthma models.
Mycobacterium vaccae (M. vaccae)	Allergy vaccines	Heat-killed M. vaccae induces Treg cells and decreases airway inflammation in atopic dermatitis or asthma murine model.
Bifidobacterium breve strain Yakult (BBG-01)	Cholera vaccine	A trend towards increased serum IgG after administration of BBG-01
Bifidobacterium longum BL999 (BL999) and Lactobacillus rhamnosus LPR (LPR)	Hepatitis B vaccine	BL999 and LPR were improved HepB surface antibody responses in subjects.
Lactobacillus paracasei ssp.	Diphtheria, tetanus and	LF19 was increased the capacity to raise immune responses in
F19 (LF19)	Hib vaccines	infants breastfed < 6 months.
LGG	Live attenuated influenza vaccines	LGG was increased protective hemagglutinin inhibition titers.
L. fermentum CECT5716 (LCECT5716)	Inactivated influenza vaccine	A trend towards increased TNF-α, total IgG and IgM, and influenza-specific IgA after administration of LCECT5716.
BB12 and L. paracasei 431 (L431)	Inactivated influenza vaccine	BB12 and L431 were elevated influenza specific IgG levels and influenza specific IgA responses.

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