Hepatitis B virus is a DNA virus that infects the liver of hominoidae (including humans) and causes hepatitis. It has caused epidemics in parts of Asia and Africa. About a third of the world's population, more than 2 billion people, have been infected with the hepatitis B virus. The acute illness causes liver inflammation, vomiting, jaundice and - rarely - death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer. This disease is preventable by vaccination (Wiki: Hepatitis B).
4. Microbial Pathogenesis
HBV primarily interferes with the functions of the liver by replicating in hepatocytes. HBV virions bind to the host cell via the preS domain of the viral surface antigen, leading to subsequent internalization through endocytosis. HBV-preS specific receptors are primarily expressed on hepatocytes. During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. The innate immune response does not play a significant role in these processes. The adaptive immune response, particularly virus-specific cytotoxic T lymphocytes (CTLs), contributes to most of the liver injury associated with HBV infection. Liver damage is initiated and mediated by the CTLs. Antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology (Wiki: Hepatitis B).
5. Host Ranges and Animal Models
Hepatitis B virus infects the liver of apes including humans (Wiki: Hepatitis B).
6. Host Protective Immunity
During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, particularly virus-specific cytotoxic T lymphocytes (CTLs), contributes to most of the liver injury associated with HBV infection. By killing infected cells and by producing antiviral cytokines capable of purging HBV from viable hepatocytes, CTLs eliminate the virus. Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver (Wiki: Hepatitis B).
II. Vaccine Related Pathogen Genes
1. envelope
Gene Name :
envelope
Sequence Strain (Species/Organism) :
Hepatitis B virus
>CAJ75787.1 preS2 middle surface protein [Hepatitis B virus]
MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVSPVPNIASHISSISSRTGDPAPTMENITSGFLGPLLVL
QAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLF
ILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTSTGPCRTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSS
WAFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYNILSPFIPLLPIFFCLWVY
I
Molecule Role :
Protective antigen
Molecule Role Annotation :
The immunological protection of pVAX-PS, a DNA vaccine, was assessed in the tree shrews model. pVAX-PS was constructed by inserting the gene encoding the middle (pre-S2 plus S) envelope protein of HBV into a plasmid vector pVAX1. Results indicated that pVAX-PS immunization could induce remarkable humoral immune response and prevent the experimental tree shrews from infection of HBV (Zhou et al., 2003).
>YP_009173869.1 large envelope protein [Hepatitis B virus]
MGQNLSTSNPLGFFPDHQLDPAFRANTANPDWDFNPNKDTWPDANKVGAGAFGLGFTPPHGGLLGWSPQA
QGILQTLPANPPPASTNRQSGRQPTPLSPPLRNTHPQAMQWNSTTFHQTLQDPRVRGLYFPAGGSSSGTV
NPVLTTASPLSSIFSRIGDPALNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGTTV
CLGQNSQSPTSNHSPTSCPPTCPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSSTTS
TGPCRTCMTTAQGTSMYPSCCCTKPSDGNCTCIPIPSSWAFGKFLWEWASARFSWLSLLVPFVQWFVGLS
PTVWLSVIWMMWYWGPSLYSILSPFLPLLPIFFCLWVYI
Molecule Role :
Protective antigen
Molecule Role Annotation :
Immunisation with a plasmid encoding the DHBV large (L) envelope protein (HBVgp2 pre-S1/pre-S2/S) induced a strong, specific, highly neutralising and long-lasting anti-preS humoral response in uninfected ducks. Importantly, maternal antibodies elicited by such DNA immunisation were vertically transmitted and protected progeny against viral challenge (Thermet et al., 2003).
>gi|21326587|ref|NP_647606.1| X protein [Hepatitis B virus]
MAARLCCQLDPARDVLCLRPVGAESRGRPVSGPFGPLPSPSSSAVPADHGAHLSLRGLPVCAFSSAGPCA
LRFTSARSMETTVNAHQVLPKVLHKRTLGLSAMSTTDLEAYFKDCLFKDWEELGEEIRLKVFVLGGCRHK
LVCSPAPCNFFPSA
Molecule Role :
Virmugen
Molecule Role Annotation :
Researchers generated a series of woodchuck hepatitis virus (WHV) X mutants. Woodchucks inoculated with X mutants, including those with no serologic evidence of infection, were protected from later challenge with infectious Woodchuck Hepatitis Virus, suggesting previous infection with resulting protective immunity (Zhang et al., 2001).
>CAJ21096.1 unnamed protein product [Hepatitis B virus]
MQWNSTTFHQTLQDPRVRGLYFPAGGSSSGTVNPVLTTASPLSSIFSRIGDPALNMENITSGFLGPLLVL
QAGFFLLTRILTIPQSLDSWWTSLNFLGGTTVCLGQNSQSPTSNHSPTSCPPTCPGYRWMCLRRFIIFLF
ILLLCLIFLLVLLDYQGMLPVCPLIPGSSTTSTGPCRTCMTTAQGTSMYPSCCCTKPSDGNCTCIPIPSS
WAFGKFLWEWASARFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYSILSPFLPLLPIFFCLWVY
I
>BAF48754.1 hepatitis B surface antigen, partial [Hepatitis B virus]
NFLGGTTVCLGQNSQSPTSNHSPTSCPPTCPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPL
IPGSSTTSTGPCRTCTTPAQGTSMYPSCCCTKPSDGNCTCIPIPSSWAFGKFLWEWASARFS
Molecule Role :
Protective antigen
Molecule Role Annotation :
Study compared a current HBV vaccine that contains recombinant hepatitis B surface antigen HBsAg) adsorbed to alum in chimpanzees, with two novel vaccine strategies that have proven superior to the current vaccine in mice. All animals receiving either control or CpG-containing subunit vaccines at 0 and 4 weeks attained titers of HBsAg-specific antibody (anti-HBs) considered protective (> or =10 mIU/ml) and were indeed protected from challenge at 8 weeks with 10(3.5) 50% chimp infectious doses (CID(50)) of intravenous HBV (Payette et al., 2006).
11. S
Gene Name :
S
Sequence Strain (Species/Organism) :
Hepatitis B virus subtype adr
>AAS47829.1 S protein [Duck hepatitis B virus]
MSGTFGGILAGLIGLLVSFFLLIKILEILRRLDWWWISLSSPKGKMQCAFQETGAQTSPHYVGSCPWGCP
GFLWTYLRLFIIFLLILLVAAGLLYLTDNGSTILGKLQWASVSALFSSISSLLPSDQKSLVALMFGLLLI
WMTSSSATQTLVTLTQLATLSALFYKS
>AGH20418.1 small S protein [Hepatitis B virus]
MENISSGLLGPLLVLQAGFFLLTKILTIPQSLDSWWTSLNFLGGTPVCLGQNSQSQISSHSPTCCPPTCP
GYRWMCLRRFIIFLCILLLCLIFLLVLLDYQGMLPVCPLIPGSSTTSTGPCRTCTTPAQGTSLFPSCCCT
KPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLSLLVPFVQWFVGHSPTVWLSVIWMMWFWGPSLYNILS
PFIPLLPIFFCLWVYI
>ACA42588.1 large S protein [Duck hepatitis B virus]
MKQESFISGYLNIWSHLKVSLIIGNSNTLSINITFMMGQHPAKSMDVRRIEGGEILLNQLAGRMIPKGTL
TWSGKFPTLDHVLDHVQTMEEINTLQNQGAWPAGAGRRVGLSNPTPQEIPQPQWTPEEDQKAREAFRRYQ
EERPPETTTIPPSSPPQWKLQPGDDPLLGNQSLLETHPLYQYTEPEPAVPVIKTPPLKKKMSGTFGGILA
GLIGLLVSFFLLIKILEILRRLDWWWISLSSPKGKMQCAFQDTGAQISPHYVGSCPWGCPGFLWTYLRLF
IIFLLILLVAAGLLYLTDNGSTILGKLQWASVSALFSSISSLLPSDPKSLVALTFGLSLIWMTSSSATQT
LVTLTQLVTLSALFYKS
Store vaccine at 2-8°C (36-46*F). Storage above or belew the recommended temperature may reduce potency. DO NOT FREEZE since freezing destroys potency (FDA COMVAX).
2. Duck hepatitis B DNA vaccine pcDNA I-S encoding small S proteins
Immune Response:
The S-DNA vaccine was able to elicit humoral immune responses against DHBV surface proteins in ducks. In addition, The S-DNA vaccine induced high titers of anti-DHBs antibodies, and anti-S antibodies induced by the S-DNA construct were highly effective in neutralizing virus infectivity. (Triyatni et al., 1998).
Efficacy:
Vaccination of ducks with S DNA vaccines prevented the development of viremia following virus challenge. All ducks were challenged with a high-titer dose of DHBV virus. Preincubation of the virus with 5, 10, or, 20 μl of anti-S serum at 37°C for 1 hour prior to i.v. inoculation into 1-day-old ducklings completely prevented the development of viremia during a 4-week observation period in all of the ducks (Triyatni et al., 1998).
ENGERIX-B contains purified surface antigen of the virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus. The surface antigen expressed in Saccharomyces cerevisiae cells is purified by several physicochemical steps and formulated as a suspension of the antigen adsorbed on aluminum hydroxide. Each 0.5-mL dose contains 10 mcg of hepatitis B surface antigen adsorbed on 0.25 mg aluminum as aluminum hydroxide (FDA: ENGERIX-B).
m. Storage
Store refrigerated between 2° and 8°C (36° and 46°F). Do not freeze.
n . Approved Age for Licensed Use
All ages
o. Contraindication
ENGERIX-B should not be administered to anyone with known hypersensitivity to any component of the vaccine, including yeast and any previous hypersensitivity to any hepatitis B-containing vaccine.
p. Description
ENGERIX-B is a sterile suspension of noninfectious hepatitis B virus surface antigen (HBsAg) for intramuscular administration. It is manufactured by GlaxoSmithKline Biologicals. It is licensed for human use in USA (FDA: ENGERIX-B).
q.
Human Response
Vaccination Protocol:
Many clinical trials were conducted on subjects ranging in ages from 6 months old to 65 years.
Side Effects:
Side Effects of vaccination with ENGERIX-B include: redness, swelling and pain of the injection site, fever, headache and dizziness
Vaccination Protocol:
Alum-adsorbed antigen, liposomes (with or without MTP-PE and with or without MDP-GDP) with HBsAg antigen or liposomes (with or without MTP-PE and with or without MDP-GDP) without HBsAg antigen, in a dose equivalent to 10 μg HBsAg were injected intramuscularly and recombinant pure HBsAg was used as control. The immunomodulator doses given with each injection were 20 μg of MTP-PE and 10 μg of MDP-GDP. Secondary immunization was done after 4 weeks with the same formulations (Jain et al., 2009).
Immune Response:
The incorporation of MTP-PE on the liposomal HBsAg increased the stimulation index (SI) four to five times as compared to plain HBsAg solution, and it also induced significantly higher Th1 cellular immune response with a predominant IFN-γ level (Jain et al., 2009).
5. HBVAXPRO
a. Manufacturer:
(Sanofi Pasteur MSD
b. Type:
Recombinant vector vaccine
c. Status:
Licensed
d. Location Licensed:
France
e. Host Species for Licensed Use:
Human
f. Antigen
hepatitis B surface antigen
g. Immunization Route
Intramuscular injection (i.m.)
h . Approved Age for Licensed Use
Patients aged ≥18 years.
i. Description
HBVAXPRO Is a recombinant vector vaccine with a single adjuvant HBV vaccine with aluminium hydroxyphosphate sulfate administered intramuscularly in the deltoid muscle. (Horta et al., 2022)
j.
Human Response
Vaccination Protocol:
Patients were vaccinated with HBVAXPRO® 40 at 0, 1 and 6 months (Horta et al., 2022).
Efficacy:
The results of our study show that HBVAXPRO is effective and safe in patients with chronic liver disease.
6. Hepatitis B DNA vaccine pCEA/HBsAg encoding CEA and HBsAg
Immune Response:
CEA-specific antibody and lymphoproliferative responses have been reported after vaccination with an anti-idiotype monoclonal antibody mimicking a portion of the CEA molecule in patients with colorectal carcinoma (Conry et al., 2002).
Efficacy:
Repetitive dosing of pCEA/HBsAg induced HBsAg antibodies in 6 of 8 patients, with protective antibody levels achieved in 4 of these patients. (Conry et al., 2002).
7. Hepatitis B DNA vaccine pCMV-HBs encoding HBsAg
Immune Response:
The serum concentration of secreted HBsAg after a one-time injection of DNA was sufficient to induce the production of anti-HBsAg 10 days after injection, and the antibody levels continued to increase for up to at least 60 days. Direct intramuscular injection of the plasmid vector encoding the HBsAg leads to secretion of the viral surface protein into the circulation, in the form of empty particles (Davis et al., 1993).
Efficacy:
A level of 10 mlU/ml of anti-HBsAg antibody is recognized as being sufficient in humans to confer protection against natural Hepatitis B virus infection. This level of antibody response was achieved in 68% of mice vaccinated with the vaccine candidate at two weeks after vaccination. By 8 wks, all mice had >100 mIU anti-HBsAg in their sera, suggesting sufficient vaccine efficacy (Davis et al., 1993).
8. Hepatitis B DNA vaccine pCMV-S2.S encoding the HBV(ayw Strain) envelope protein.
Immune Response:
Immunization of chimpanzees with HBsAg-expressing plasmid DNA induced specific anti-HBs antibodies. The higher dose of DNA (2 mg) induced significant titers (>100 mIU/ml) of anti-HBs after the initial injection of DNA. These titers never went below the 10 mIU/ml level considered adequate to confer protection (Davis et al., 1996).
Efficacy:
The outcome of challenge with live HBV of the ayw strain was strongly correlated with the anti-HBs titers. Of the eight chimpanzees with a titer >10 mIU/ml, all were protected from infection except for one, which had the lowest anti-HBs titer at 12 mIU/ml. These findings agree closely with the critical protective level of 10 mIU/ml determined for humans by the Centers for Disease Control (Davis et al., 1996).
9. Hepatitis B DNA vaccine PLGA–CTAB–DNA encoding the small envelope gene
Immune Response:
PLGA–CTAB–DNA optimizes two key features during antigen presentation, controlled release and targeted delivery, which might be involved in the mechanisms of its augmented immunogenicity and enhanced immunoprotection (He et al., 2005)
Challenge Protocol:
Challenge with transplanted HBsAg-expressing tumor cells (He et al., 2005).
Efficacy:
Mice immunized with PLGA–CTAB–pVAX(S) (20 μg per mouse) or naked pVAX(S) (100 μg per mouse) after a challenge of transplanted HBsAg-expressing tumor cells showed weak protection efficacy, resulting in a final survival rate of 10% or 20% at week 15. However, mice immunized with PLGA–CTAB–pVAX(S) at the dose of 100 μg per mouse displayed a strong inhibition on tumor formation and a remarkable improvement in final survival rate (60%) (He et al., 2005).
10. Hepatitis B DNA vaccine pRc/CMV-HBs(S) encoding HBsAg
Immune Response:
When mice are immunized with recombinant HBsAg, the main type of immune response generated is the antibody response. However, a Th1/CTL response was also elicited, which is important to facilitate eradication of HBV infection and can be utilized for therapeutic immunization of HBV chronic carriers (Khatri et al., 2008).
Efficacy:
Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level (>10 mIU/ml) suggesting successful generation of systemic immunity. Levels of 1 and 10 mIU/ml are well-established standards for anti-HBs antibody levels in mice and humans, respectively and are considered sufficient to confer protection against the disease (Khatri et al., 2008).
11. Hepatitis B DNA vaccine pS encoding major envelope proteins
Immune Response:
Coexpression of IL-2 and hepatitis B virus HBV^3 envelope protein within the same plasmid vector resulted in a dramatic increase in its ability to induce humoral and cellular immune responses to HBsAg. Also, the IL-2 adjuvant activity helps the HBV DNA vaccine elicit high anti-HBs titers in animals that usually fail to respond to rHBsAg vaccination (Chow et al., 1998)
Efficacy:
Four of five mice immunized with pS + pcDNA3 and challenged with CT26/S showed an inhibition of tumor growth. The protective efficacy was dramatically increased when the IL-12 gene was coinjected with plasmid pS because tumor growth was significantly suppressed, and two of five mice remained tumor free up to 60 days following tumor challenge (Chow et al., 1998).
12. Hepatitis B surface antigen (HBsAg) with JVRS-1000
Vaccination Protocol:
HBV transgenic mice were vaccinated with HBsAg (i.m., 5 μg), or HBsAg plus JVRS-100 (i.v., 10 μg) in female C57BL/6 mice (>6 weeks). Animals were treated on days 1, 22, and 43 (Morrey et al., 2011).
Immune Response:
JVRS-100 combined with hepatitis B surface antigen (HBsAg) broke tolerance by stimulating significant B and T cell responses. The combination of HBsAg + JVRS-100 elicited a T cell response as indicated by increased levels of IFN-γ in splenocyte cell-culture supernatant (Morrey et al., 2011).
13. Hepatitis B virus DNA vaccine encoding HBVgp2 pre-S1/pre-S2/S
Description:
The pCI expression vector (Promega, Charbonières, France) was used to clone the entire DHBV large envelope gene into Not I polylinker site leading to the pCI-preS/S plasmid [5] and the DHBV core gene leading to pCI-C plasmid (Thermet, submitted). The pCI-preS/S, pCI-C and the native pCI plasmids were purified by Endotoxin Free Giga prep (Qiagen, Hilden, Germany) (Thermet et al., 2003).
Vaccination Protocol:
Four-week-old ducks received intramuscular (i.m.) injections of 100–300 μg of plasmid DNA diluted in NaCl 0.9%. The birds were injected in three sites (anterior quadriceps of both legs and breast), and booster doses were given 3 weeks later at the same sites (Thermet et al., 2003).
Challenge Protocol:
Progeny ducklings received a high titre DHBV challenge and the viremia was followed by quantitative dot blot hybridisation for each animal during 17 days (Thermet et al., 2003).
Efficacy:
Immunisation with a plasmid encoding the DHBV large (L) envelope protein (HBVgp2 pre-S1/pre-S2/S) induced a strong, specific, highly neutralising and long-lasting anti-preS humoral response in uninfected ducks. Importantly, maternal antibodies elicited by such DNA immunisation were vertically transmitted and protected progeny against viral challenge (Thermet et al., 2003).
Description:
pVAXPS was constructed by inserting the gene encoding the middle (pre-S2 plus S) envelope protein of HBV into a plasmid vector pVAX1 (Zhou et al., 2003).
Vaccination Protocol:
Sixty adult tree shrews purchased from the Kunming Animal Institute were randomly divided into four groups and immunized twice at 2-week intervals with the DNA vaccine by i.m. injection of 100 mg of pVAX-PS or pVAX1 in a volume of 100 ml in bilateral quadriceps (Zhou et al., 2003).
Challenge Protocol:
Two weeks after the second DNA immunization, tree shrews in two groups (immunized with pVAX-PS and pVAX1, respectively) were challenged through the caudal vein with 0.8 ml of the patient’s serum positive for the HBV marker (Zhou et al., 2003).
Efficacy:
The immunological protection of pVAX-PS, a DNA vaccine, was assessed in the tree shrews model. pVAX-PS was constructed by inserting the gene encoding the middle (pre-S2 plus S) envelope protein of HBV into a plasmid vector pVAX1. Results indicated that pVAX-PS immunization could induce remarkable humoral immune response and prevent the experimental tree shrews from infection of HBV (Zhou et al., 2003).
Persistence:
An X protein mutant is attenuated in woodchucks (Zhang et al., 2001).
Efficacy:
An X protein mutant induces significant protection in woodchucks from challenge with wild type Hepatitis B virus (Zhang et al., 2001).
16. Infanrix-hexa
a. Product Name:
Combined diphtheria and tetanus toxoids, acellular pertussis, hepatitis B (recombinant), inactivated poliomyelitis and adsorbed conjugated Haemophilus influenzae type b vaccine
Polymyxin B Neomycin, Latex in plunger stopper of prefilled syringe
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
The vaccine should be refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.
o . Approved Age for Licensed Use
PEDIARIX is indicated for active immunization against diphtheria, tetanus, pertussis (whooping cough), all known subtypes of hepatitis B virus, and poliomyelitis caused by poliovirus Types 1, 2, and 3 as a three-dose primary series in infants born of HBsAg-negative mothers, beginning as early as 6 weeks of age. PEDIARIX should not be administered to any infant before the age of 6 weeks, or to individuals 7 years of age or older (FDA: Pediarix).
p. Description
Products: Proteins + killed virus. Other components: Yeast protein Formaldehyde, Polysorbate 80.
18. recombinant S gene Hepatitis B Vaccine with rIFN-gamma
Vaccination Protocol:
81 adult white hemodialysis patients (46 men, 35 women aged 19-65 yrs) with no serological evidence of immunity to hepatitis B were used in the study. Patients were randomly allocated to one of two groups. Group I comprised 41 patients who recieved 40μg of recombinant (S gene) hepatitis B vaccine by i.m. injection and 0,1, and 6 months. Group II comprised 40 patients who received 40 μg of recombinant (S gene) hepatitis B vaccine given intramuscularly with 2 million units (MU) of rIFN-gamma/m^2 body surface given subcutaneously at 0,1, and 6 months (Quiroga et al., 1990).
Immune Response:
The titers of anti-HBs achieved among patients who received vaccine and rIFN-gamma were higher than among those receiving the vaccine alone (Quiroga et al., 1990).
RECOMBIVAX HB is a sterile suspension for intramuscular injection. It is a non-infectious subunit viral vaccine derived from hepatitis B surface antigen (HBsAg) produced in yeast cells. A portion of the hepatitis B virus gene, coding for HBsAg, is cloned into yeast, and the vaccine for hepatitis B is produced from cultures of this recombinant yeast strain according to methods developed in the Merck Research Laboratories. The antigen is harvested and purified from fermentation cultures of a recombinant strain of the yeast Saccharomyces cerevisiae containing the gene for the adw subtype of HBsAg (Merck: Recombivax HB).
m. Storage
Store vials and syringes at 2-8°C (36-46°F). Do not freeze.
n . Approved Age for Licensed Use
All ages
o. Contraindication
RECOMBIVAX-HB should not be administered to anyone with a known hypersensitivity to yeast or any component of the vaccine.
p.
Human Response
Side Effects:
Side effects included: pain, redness and swelling of the injection site, fatigue, fever, headache and nausea.
20. Twinrix
a. Product Name:
Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine
TWINRIX is a sterile suspension of inactivated hepatitis A virus (strain HM175) propagated in MRC-5 cells, and combined with purified surface antigen of the hepatitis B virus.
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
TWINRIX should be refrigerated between 2° and 8° C (36° and 46° F). Do not freeze.
n . Approved Age for Licensed Use
Ages 18 and older
o. Contraindication
TWINRIX should not be administered to anyone with known hypersensitivity to any component of the vaccine, including yeast and neomycin and in patients with previous hypersensitivity to TWINRIX or monovalent hepatitis A or hepatitis B vaccines (FDA: TWINRIX).
p.
Human Response
Immune Response:
In clinical trials, it has been found that combining the hepatitis A antigen with the hepatitis B surface antigen in TWINRIX resulted in comparable anti-HAV or anti-HBsAg titers, relative to vaccination with the individual monovalent vaccines or the concomitant administration of each vaccine in opposite arms (FDA: TWINRIX).
Side Effects:
Side effects of immunization included: redness, itching and swelling of the injection site, headache and fatigue. Severe adverse effects were limited and resolved in a timely matter.
Products: Recombinant protein + killed virus. Other components: Yeast protein Formaldehyde, Polysorbate 20.
IV. References
1. Chen et al., 2011: Chen JH, Yu YS, Liu HH, Chen XH, Xi M, Zang GQ, Tang ZH. Ubiquitin conjugation of hepatitis B virus core antigen DNA vaccine leads to enhanced cell-mediated immune response in BALB/c mice. Hepatitis monthly. 2011; 11(8); 620-628. [PubMed: 22140385].
2. Chow et al., 1998: Chow YH, Chiang BL, Lee YL, Chi WK, Lin WC, Chen YT, Tao MH. Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. Journal of immunology (Baltimore, Md. : 1950). 1998; 160(3); 1320-1329. [PubMed: 9570550].
3. Conry et al., 2002: Conry RM, Curiel DT, Strong TV, Moore SE, Allen KO, Barlow DL, Shaw DR, LoBuglio AF. Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and hepatitis B surface antigen in colorectal carcinoma patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2002; 8(9); 2782-2787. [PubMed: 12231517].
4. Davis et al., 1993: Davis HL, Michel ML, Whalen RG. DNA-based immunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating antibody. Human molecular genetics. 1993; 2(11); 1847-1851. [PubMed: 8281146].
5. Davis et al., 1996: Davis HL, McCluskie MJ, Gerin JL, Purcell RH. DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proceedings of the National Academy of Sciences of the United States of America. 1996; 93(14); 7213-7218. [PubMed: 8692971].
12. Hwang et al., 2002: Hwang YK, Kim NK, Park JM, Lee K, Han WK, Kim HI, Cheong HS. HLA-A2 1 restricted peptides from the HBx antigen induce specific CTL responses in vitro and in vivo. Vaccine. 2002; 20(31-32); 3770-3777. [PubMed: 12399208].
13. Jain et al., 2009: Jain V, Vyas SP, Kohli DV. Well-defined and potent liposomal hepatitis B vaccines adjuvanted with lipophilic MDP derivatives. Nanomedicine : nanotechnology, biology, and medicine. 2009; 5(3); 334-344. [PubMed: 19523433].
14. Khatri et al., 2008: Khatri K, Goyal AK, Gupta PN, Mishra N, Vyas SP. Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. International journal of pharmaceutics. 2008; 354(1-2); 235-241. [PubMed: 18182259].
15. Kuhröber et al., 1997: Kuhröber A, Wild J, Pudollek HP, Chisari FV, Reimann J. DNA vaccination with plasmids encoding the intracellular (HBcAg) or secreted (HBeAg) form of the core protein of hepatitis B virus primes T cell responses to two overlapping Kb- and Kd-restricted epitopes. International immunology. 1997; 9(8); 1203-1212. [PubMed: 9263018].
16. Kwissa et al., 2003: Kwissa M, Kröger A, Hauser H, Reimann J, Schirmbeck R. Cytokine-facilitated priming of CD8+ T cell responses by DNA vaccination. Journal of molecular medicine (Berlin, Germany). 2003; 81(2); 91-9101. [PubMed: 12601525].
18. Morrey et al., 2011: Morrey JD, Motter NE, Chang S, Fairman J. Breaking B and T cell tolerance using cationic lipid-DNA complexes (CLDC) as a vaccine adjuvant with hepatitis B virus (HBV) surface antigen in transgenic mice expressing HBV. Antiviral research. 2011; 90(3); 227-230. [PubMed: 21545812].
19. Payette et al., 2006: Payette PJ, Ma X, Weeratna RD, McCluskie MJ, Shapiro M, Engle RE, Davis HL, Purcell RH. Testing of CpG-optimized protein and DNA vaccines against the hepatitis B virus in chimpanzees for immunogenicity and protection from challenge. Intervirology. 2006; 49(3); 144-151. [PubMed: 16428890].
20. Qing et al., 2010: Qing Y, Chen M, Zhao J, Hu H, Xu H, Ling N, Peng M, Ren H. Construction of an HBV DNA vaccine by fusion of the GM-CSF gene to the HBV-S gene and examination of its immune effects in normal and HBV-transgenic mice. Vaccine. 2010; 28(26); 4301-4307. [PubMed: 20430121].
21. Quiroga et al., 1990: Quiroga JA, Castillo I, Porres JC, Casado S, Sáez F, Gracia Martínez M, Gómez M, Inglada L, Sánchez-Sicilia L, Mora A. Recombinant gamma-interferon as adjuvant to hepatitis B vaccine in hemodialysis patients. Hepatology (Baltimore, Md.). 1990; 12(4 Pt 1); 661-663. [PubMed: 2145212].
22. Schirmbeck et al., 1995: Schirmbeck R, Böhm W, Ando K, Chisari FV, Reimann J. Nucleic acid vaccination primes hepatitis B virus surface antigen-specific cytotoxic T lymphocytes in nonresponder mice. Journal of virology. 1995; 69(10); 5929-5934. [PubMed: 7666497].
23. Tacket et al., 1999: Tacket CO, Roy MJ, Widera G, Swain WF, Broome S, Edelman R. Phase 1 safety and immune response studies of a DNA vaccine encoding hepatitis B surface antigen delivered by a gene delivery device. Vaccine. 1999; 17(22); 2826-2829. [PubMed: 10438052].
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