Hepatitis B Vaccine And Preventing Hpv Biology Essay


Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels of antibodies to hepatitis B surface antigen (anti‐HBs) and are considered to be nonresponders. (Cardell, 2008) Hepatitis B is a serious disease that affects the liver. This is caused by the Hepatitis B virus (HBV). This disease can cause acute illness such as loss of appetite, diarrhea and vomiting, tiredness, jaundice (yellow skin or eyes), pain in muscles, joints and stomach. This is more common among adults than children. Children who usually get infected don't have acute illness. Children go through chronic infection which is a long-term infection which often leads to liver damage, liver cancer or death. HBV can be spread to other even if the symptoms aren't visible. This disease is spread through contact with the blood or other body fluids of an infected person. In 2005, about 51,000 people became infected with hepatitis B. (CDC, 2007) About 1.25 million people in the United States have chronic HBV infection.(CDC, 2007) Each year about 3,000 to 5,000 people die from cirrhosis or liver cancer caused by HBV. (CDC, 2007) As you can see even though people are taking the vaccine during childhood they are still getting infected and many people are dying because the vaccine is not responding. So Kristina Cardell from the department of infectious diseases and clinical microbiology came up with a new hypothesis saying that with a double dose of the combined hepatitis A virus and B vaccine were given to the people who were nonresponders of the original hepatitis b virus will be highly effective.

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In 1982 the first hepatits B vaccine became commercially availabline in the United States and in 1986 a hepatitis B vaccine produced by recombinant DNA technology was licensed, and a second recombinant-type hepatitis B vaccine was licensed in 1989. (IAC, 2008) Recombivax HB and Engerix-B are the two vaccines for the hepatitis B. These vaccines are recombinant DNA vaccines meaning that they are produced by inserting the gene for HBV into common baker's yeast where it is grown, harvested and purified.( ) The vaccine is made from inactivated whole virus of hepatitis B. The inactive virus stimulates your body to produce antibodies to fight the hepatitis B virus. (Dugdale, 2009) This vaccine is given to infants 12 months and under in the thigh muscle or the upper arm muscle. Hepatitis B vaccine is a three-dose series and is recommended for all children 0-18 years old. Most states require hepatitis B vaccine for school entry. Adolescents who are just starting their series will need two or three doses, depending on their age and the brand of vaccine used. Adults at increased risk of acquiring HBV infection should also be vaccinated. In addition, the vaccine can be given to any person who desires protection from hepatitis B. (IAC, 2008)

In Kristina Cardell's experiment to combine the hepatitis A and B vaccine she used health care workers who were known to be nonresponders to the hepatitis B vaccine. This study was approved by the Ethics Committee of the Health University, Linkoping, Sweden. All the subjects for this experiment were negative for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, anti-HBs, and anti-HAV before inclusion. (Cardell, 2008) All the subjects were vaccinated intramuscularly at 0, 1, and 6 months with 2.0 mL of combined hepatitis A and B vaccine (Twinrix; GlaxoSmithKline) at the Department of Infectious Diseases, University Hospital, Linkopling. (Cardell, 2008) Blood samples were drawn 5 times during the study period. Once before the first dose, immediately before the second and 1 month after the second dose. And then immediately before the third dose, and 1 month after the third dose. (Cardell, 2008) There was a registered questionare after each dose.

This study was designed as an open trial. Her estimation was that, with the study group of 50 nonresponders and a reference group of 20 previously unvaccinated healthy individuals it would be able to show the differences between the groups (not the similarities), and the reference group would show whether the vaccination schedule would work in a normal population. They used the t test to distinguish the differences in demographic data between the groups. They also analyzed the influence of such cofactors as smoking, age, BMI and sex on the results. She used the a general linear model for that analysis. The model was chosen by starting with a full model that included all interactions allowed by the data and then reducing the interactions. It started from the highest order stepwise and then reducing the main effects if they were not part of the interactions. (Cardell, 2008)

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In the beginning there were a total of 48 nonresponders who were enrolled, and out of that 44 completed the study. The other 4 didn't complete due to personal circumstances. Twenty healthy HAV- and HBV-nonimmune adults were enrolled in the reference group, all of which completed the study. (Cardell, 2008) There were no serious adverse events seen in the nonresponder group and the reference group.


table1.Summary of demographic data.


Sex, no. male/female

Age, mean (range), years

BMI, mean (range)

Smoking, no.



50 (21-69)

25.5 (20.1-35.6)


Reference group


34 (20-59)

24.4 (19.3-30.9)







Note.BMI, body mass index.

This is the demographic data. There were a majority of women in the reference group and the nonresponder group. All the people were either health care workers or students in health care science. In the nonresponder group, 13 were smokers and in the reference group there was only 1 smoker. The mean BMI was higher in the nonresponder group than in the reference group. Also the mean age was also higher in the nonresponder group than the reference group.

Figure1.No. of vaccinees who achieved a protective level (10 mIU/mL) of antibodies to hepatitis B surface antigen (anti‐HBs) after each dose in the nonresponder group and in the reference group. P values for differences in the response rate between the 2 groups are given (Fisher's exact test).

Figure1.No. of vaccines who achieved a protective level (10 mIU/mL) of antibodies to hepatitis B...

From the 44 nonresponders, 26(59%), 35 (80%), and 42 (95%) developed anti-HBs levels of >10 mIU/mL after the first dose, the second dose, and the complete 3-dose schedule. (Cardell, 2008) In the reference group, the corresponding figures were 2 (10%) of 20, 19 (95%) of 20, and 20 (100%) of 20. (Cardell, 2008) Of the 2 nonresponders, 1 did not have a detectable anti‐HBs level, and 1 had an anti‐HBs level of 8.5 mIU/mL. Both of these individuals were smokers. After 3 doses, a total of 35 nonresponders (80%) developed anti‐HBs titers of >100 IU/mL. All subjects in the reference group had an anti‐HBs titer of >100 IU/mL after 3 doses.(Cardell, 2008)

Figure2.Levels of antibodies to hepatitis A virus (HAV) after each dose in the nonresponder group and in the reference group. Lines indicate medians. The difference in anti‐HAV level between the reference group and the nonresponder group after 3 doses was statistically significant ( , Mann‐Whitney rank‐sum test).

Figure2.Levels of antibodies to hepatitis A virus (HAV) after each dose in the nonresponder group ...

The subjects in both the groups responded to the hepatitis A vaccine and developed anti-HAV.

Figure3.Levels of antibodies to hepatitis B surface antigen (anti‐HBs) after each dose in the nonresponder group and in the reference group. Lines indicate medians. P values for differences in anti‐HBs level after each dose between the 2 groups are given (Mann‐Whitney rank‐sum test).

Figure3.Levels of antibodies to hepatitis B surface antigen (anti‐HBs) after each dose in the nonr...

In Figures 2 and 3 its shows the Anti-HAV and anti-HBs levels after each dose of all the subjects. The median is marked for all doses and groups.

The data shows that the previous nonresponders show an anmnestic response to revaccination, saying that more subjects developed protective anti-HBs levels after the first injection. Even thought there was an absence of protective levels of anti-HBs from the previous vaccination, the immune systems of the subjects were primed to HBsAg, saying that they may have been protected against infection. (Caredll, 2008) The present revaccination schedule was highly effective in inducing seroconversion, given that there was no statistical difference in frequency after 3 doses (42/44 vs. 20/20; difference not significant). But the anti‐HBs as well as anti‐HAV levels were significantly lower in the nonresponder group than in the reference group. This means that that nonresponder status with respect to HBsAg may not be an isolated immunological event but rather reflect a more general phenomenon. (Cardell, 2008)

When they were analyzing the influence of the other factors, she found that both a high BMI and smoking was associated with lower anti-HBs levels and that a high BMI was associated with lower anti-HAV levels. These effects were more in the nonresponder group than the reference group for both anti-HBs and anti-HAV.

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Her results say that a high dose of HBsAg in combination with the hepatitis A antigen could offer a clinically relevant approach to correcting nonresponder status in people who are not already immune to hepatitis A and for whom protection against hepatitis B is essential. (Cardell, 2008) It has been shown that, in healthy individuals, anti-HBs levels are higher when the combined vaccine is used than when a vaccine containing HBsAg alone is used.

Kristina Cardell, Britt Åkerlind, Matti Sällberg, and Aril Frydén, 2008, "Excellent Response Rate to a Double Dose of the Combined Hepatitis A and B Vaccine in Previous Nonresponders to Hepatitis B Vaccine", The Journal of Infectious Disease, 198:299-304


Lemon SM, Thomas Dl, Vaccines to prevent viral hepatitis, 1997, 336:196-204

I Desombere, P Hauser, R Rossau, J Paradijs and G Leroux-Roels, 1995, "Nonresponders to hepatitis B vaccine can present envelope particles to T lymphocytes," The Journal of Immunology, Vol 154, Issue 2 520-529



Levitz RE, Cooper BW, Regan HC, 1995, "Immunization with high‐dose intradermal recombinant hepatitis B vaccine in healthcare workers who failed to respond to intramuscular vaccination," Infect Control Hosp Epidemiol,16,88-91.