GSK'S Innovative Adjuvant In Candidate HPV Vaccine (Cervarixtm) Induces Stronger & Sustained Immune Response Compared To Conventional Adjuvant

The immune response against the virus that causes cervical cancer is stronger and sustained following vaccination with GlaxoSmithKline's (GSK) candidate HPV vaccine formulated with the innovative AS04 adjuvant compared to using the same vaccine formulated with a conventional aluminium salt adjuvant. 1


Data from the first studies to directly compare two different formulations of GSK's HPV vaccine has revealed that the antibody response induced by the vaccine formulated with the innovative AS04 adjuvant was higher, compared to the same vaccine formulated with a conventional aluminium salt adjuvant. This enhanced immune profile observed with the AS04 formulation was shown to persist for at least 3.5 years post-vaccination. 1


Furthermore, these data, published in Vaccine, showed that the AS04 adjuvanted vaccine also induced a more robust immune memory response - specifically, the AS04 formulation elicited an increased number (2.5 to 5.2 fold) of HPV 16/18 specific memory B-cells - compared to that observed after vaccination with the same vaccine formulated with a conventional aluminium salt adjuvant.


In previously published studies, GSK's HPV vaccine, formulated with the innovative AS04 adjuvant, has demonstrated sustained efficacy up to 4.5 years against HPV 16/18 infections, associated abnormal cytology and precancerous lesions (CIN). 2,3


Clinical trials are currently ongoing to determine the duration of protection that results from HPV vaccination. They aim to establish whether the higher antibody levels seen following vaccination with the AS04 adjuvanted HPV vaccine will have a positive impact on long term protection.


Dr Philippe Monteyne, Head of Global Vaccine Development of GSK Biologicals, said: "For a HPV vaccine to be effective, it must induce a strong immune response and provide protection that lasts. These new data demonstrate a genuine immunological benefit with the AS04 adjuvant by contributing to a strong and sustained vaccine-induced immune response of high quality."


What is an adjuvant?


The word adjuvant comes from the Latin word adjuvare which means 'to help'.


Adjuvants are substances, which when used in combination with antigens in vaccines, enhance the immune response. The use of adjuvants in vaccines is very common. Vaccines have conventionally been formulated with aluminium salt as the adjuvant.


About GSK's AS04 adjuvant


GSK's candidate HPV vaccine is formulated with the innovative adjuvant AS04. AS04 is composed of aluminium salt and monophosphoryl lipid A (MPL). MPL is an immunostimulant, capable of directly activating key immune mechanisms. The combination of aluminium salt and MPL has been shown, in these studies, to further enhance the immune response to antigens included in the vaccine compared to aluminium salt alone.


About the studies















In these studies, GSK's HPV vaccine, formulated with the innovative AS04 adjuvant, and the same vaccine formulated with a conventional aluminium salt adjuvant were compared to assess the quality of the immune response generated after vaccination.


In human studies, subjects received a three-dose course (at 0, 1 and 6 months) of GSK's HPV vaccine formulated with either the innovative AS04 adjuvant or a conventional aluminium salt adjuvant. Following vaccination, antibody levels and immune memory B-cells were measured.


Results in human subjects showed that enhanced antibody levels induced by the AS04 adjuvanted HPV vaccine were 1.5 and 2.1 times higher for HPV 16 and HPV 18 respectively, at 3.5 years post-vaccination, compared to those induced following vaccination with the same vaccine formulated with a conventional aluminium salt adjuvant.



The studies also demonstrated the ability of the AS04 adjuvanted vaccine to increase the number of immune memory B-cells. One month following completion of a three-dose course of GSK's HPV vaccine formulated with the innovative AS04 adjuvant, observed numbers of memory B-cells were 2 and 3.6 times higher for HPV 18 and HPV 16 respectively than those observed following vaccination with the same vaccine formulated with a conventional aluminium salt adjuvant. Recent observations have indicated that immune memory B-cells play a key role in the persistence of antibody levels following vaccination.


Full results of the studies may be viewed online at:
sciencedirect or Vol. 24 of Vaccine, publication date 14 August 2006.


About GSK's candidate HPV vaccine


GSK's HPV vaccine has been developed to prevent infection and precancerous lesions caused by the two most common HPV types associated with cervical cancer, HPV 16 and 18. In addition, GSK's candidate HPV vaccine has shown protection against incident infection with the third and fourth most common HPV types associated with cervical cancer, HPV 45 and 31. 2,3 HPV types 16, 18, 45 and 31 are collectively responsible for approximately 80 per cent of cervical cancers globally. 2,3


GSK submitted a marketing application for its HPV vaccine to the European Agency for the Evaluation of Medicinal Products (EMEA) in March 2006.


An ongoing Phase III clinical trials programme involving more than 30,000 women worldwide continues.


About HPV and cervical cancer


Cervical cancer and precancerous lesions together represent a significant health and psychological burden for women in the UK. 4-9


In the UK each year, almost 3,000 new cases of cervical cancer are reported 5 and there are more than 1,000 deaths. 4 It is the second most common cancer in women under the age of 35 years.5


Cervical cancer is not hereditary. It is caused by high risk types of human papillomavirus (HPV). Two high risk types of the virus, HPV 16 and 18, together cause approximately 70 per cent of cervical cancers. 12


Anyone who has had a sexual relationship is at risk of infection with HPV, as it is very common and easily transmitted through skin to skin contact in the genital area. 13-14 Up to 80 per cent of sexually active women will be infected with a type of HPV at some point in their lives. 16-17


Most infections will be cleared naturally but, if infection persists, women are at risk of developing cervical cancer. It is not possible to predict which women with persistent infection will go on to develop precancerous lesions and/ or cancer. 17


Risk of exposure to high risk HPV can continue throughout a sexually active woman's life 18 and prior HPV infection may not always provide sufficient immunity to protect against subsequent infections. 12, 13, 19, 20


Detection and treatment of precancerous lesions through screening has reduced cervical cancer incidence and mortality in the UK, highlighting the importance of attending regular cervical screening. 6


It has been estimated that without a screening programme, up to 5,000 more UK women would die each year from cervical cancer. 21


About GlaxoSmithKline and GlaxoSmithKline Biologicals


GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information please visit gsk.


GSK Biologicals (GSK Bio), one of the world's leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline's activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide.


In 2005, GSK Bio distributed more than 1.2 billion doses of vaccines to 165 countries in both the developed and the developing world, an average of more than 3 million doses per day.


References


1. Giannini SL et al. Vaccine 2006

2. Harper D et al. Lancet 2006; 367: 1247-1255

3. Harper D et al. Lancet 2004;364:1757-65

4. Ferlay J et al. Globocan 2002: Cancer incidence, mortality and prevalence worldwide. IARC Cancerbase No. 5. Version 2.0, IARC Press, Lyon, 2004. www.depdb.iarc.fr/globocan/GLOBOframe.htm

5. CancerStats Jan 2003

6. Cervical Screening Programme England 2004/5. National Statistics Bulletin 2005/09/HSCIC

7. Office of National Statistics. Cancer registration statistics 2002

8. Rogstad KE. BJOG 2002; 109 (4):364-8

9. Peto J et al. British Journal of Cancer 2004; 91: 942-953

10. Walboomers J et al. J Pathol 1999; 189: 12-19

11. Bosch FX et al. J Clin Pathol 2002; 55: 244-65

12. Munoz N et al. Int J Cancer 2004; 111: 278-85

13. Baseman J and Koutsky L. J Clin Virol 2005

14. Winer et al. Am J Epidemiol 2003; 157(3): 218-26

15. Koutsky L. American Journal of Medicine 1997; 102 (5A); 3-8

16. Moscicki A-B et al. J Pediatr 1998: 132: 277-84

17. Choma K. Am J Nursing 2003; 103(2): 42-50

18. Grainge et al. Em Infect Dis 2005; 11 (11): 1680-1685

19. De Jong A et al. Cancer Res 2004; 64: 5449-55 20. Franco EL and Harper DM. Vaccine 2005; 23: 2388-94

21. Peto et al. Lancet 2004 (July 17); 364: 249-256

New Mothers Benefit From Community-Based Internet Forums But Fathers Could Be Marginalized

Researchers believe that local online forums could play a key role in helping new mothers to share experiences and concerns, according to a study published in the January issue of the UK-based Journal of Advanced Nursing.



Professor Wendy Hall from the University of British Columbia and Assistant Professor Valerie Irvine from the University of Victoria, Canada, studied online communication threads between a group of 40 women, who had all given birth in the same year and joined a local forum based in a moderate-sized Canadian city.



They concluded that these forums could provide a viable alternative to face-to-face groups, especially in rural communities where travel and professional support are limited.



As a result of the study, the researchers are encouraging healthcare professionals to help mothers with young children to set up, or access, similar community-based networks as they believe they offer more tailored support than existing corporate web-based forums with unlimited international access.



But they have warned that there is a danger that women-only forums can marginalise fathers and that if fathers are not actively involved in discussions about childcare this could pose particular problems for working mothers.



"The 12 women who initially set up the forum met while they were attending parent education classes" explains Professor Hall. "They invited a community health nurse to monitor their communications and correct any information that was wrong."



New members were then invited by word of mouth.



The 40 women who took part in the study gave the researchers permission to monitor their archived posts, which covered a one-year period. They were highly educated, with an average age of 36. The group included pregnant women as well as the mothers of babies up to 11 months of age. Eight out of ten were married and 88 per cent had above average incomes. Sixty-one per cent were employed outside the home, nine per cent worked at home for pay and 14 per cent were on maternity leave.



The researchers found that the women used the online support group to:
Develop community connections in the small geographical area that the membership covered. It was used to share information about accessing community programmes and classes, suggest and share the names of service providers, organise dates for events, sell or trade children's items, share videos and plan get-togethers.


Request and provide emotional support. The women shared their stories, experiences and feelings, expressed sympathy, thanked others for their help and talked about their beliefs and expectations. For example they discussed practical issues, like breastfeeding, finding child care, teething and healthcare experiences, and emotional issues, like how they felt about going back to work.


Share information that they had gleaned from websites, reading or care providers, and learn. For example, they talked about the best ways to get their babies to sleep, useful websites and books they had discovered or advice they had been given by their healthcare provider on issues such as milk allergies. They also helped other members whose computer skills were less developed.















Normalise the experiences they were having with their babies and as mothers. The women found it helpful to discuss problems and compare notes about problems as it made them realise that other mothers had similar issues. They also talked about how they had solved problems, the advice they had received and how their experiences would change as their children developed.

The authors have pointed out that the experiences of mothers on a tightly-knit geographical forum could be more similar than women on a website that draws membership from diverse communities across the world.



"The mothers who became part of this online community obviously drew great benefits from the advice, support and friendship they received from other local women" says Professor Hall.



"However some of the women did report that their partners were commenting on how much time they spent on the computer and they acknowledged that social activities were organised that excluded fathers.



"There were some indications that our study group felt that parenting was primarily their responsibility and that fathers didn't need to be included in the discussions. Supporting mothers is very important but it is also vital that fathers are not sidelined in a way that discourages them from being active parents."



The authors conclude that local online support groups can play an important role in helping to support women in what can be an isolating experience, by bringing them together with other mothers with similar expectations, beliefs and knowledge.



"This self-sufficient grass-roots group required limited monitoring by the community health nurse and this format could offer an alternative to face-to-face support groups" says Professor Hall. "Nurses and other healthcare providers could also help women to identify online local or regional resources.



"The forum we studied clearly shows that the opportunity to share experiences with like-minded, local women can stop pregnant women and mothers from feeling isolated and worrying about giving birth and parenting."







Notes:
E-communication among mothers of infants and toddlers in a community-based cohort: a content analysis. Hall W and Irvine V. Journal of Advanced Nursing. 65.1 pp 175-183 (January 2009).


Journal of Advanced Nursing is read by experienced nurses, midwives, health visitors and advanced nursing students in over 80 countries. It informs, educates, explores, debates and challenges the foundations of nursing health care knowledge and practice worldwide. Edited by Professor Alison Tierney, it is published 24 times a year by Blackwell Publishing Ltd, part of the international Blackwell Publishing group. journalofadvancednursing



About Wiley-Blackwell: Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley's Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit blackwellpublishing/ or interscience.wiley/.

Source: Annette Whibley


Wiley-Blackwell

Michigan Senate Approves Bills That Would Require Girls To Receive HPV Vaccine Before Entering Sixth Grade

The Michigan Senate on Wednesday voted 36-1 to approve two bills (SB 1416, SB 1417) that would require girls in the state entering the sixth grade in the 2007-2008 school year and beyond to have received Merck's human papillomavirus vaccine Gardasil, the AP/Detroit Free Press reports (AP/Detroit Free Press, 9/20). FDA in July approved Gardasil for sale and marketing to girls and women ages nine to 26. According to Merck, the vaccine -- which is given in three injections over six months and costs $360 -- in clinical trials has been shown to be 100% effective in preventing HPV infection with strains 16 and 18, which together cause about 70% of cervical cancer cases, in women who do not already have the virus, and about 99% effective in preventing HPV strains 6 and 11, which together with strains 16 and 18 cause about 90% of genital wart cases. Gardasil also protects against vaginal and vulvar cancers, two other gynecological cancers that are linked to HPV, according to a study presented in June at a meeting of the American Society of Clinical Oncology in Atlanta. CDC's Advisory Committee on Immunization Practices in July recommend that all girls ages 11 and 12 receive the vaccine and that Gardasil be covered by the Vaccines for Children Program, which provides no-cost immunizations to children covered by Medicaid, Alaska-Native and American Indian children, and some uninsured and underinsured children. Health insurers Aetna, Cigna and WellPoint have said they will offer coverage for Gardasil.

Bill Details, Debate
The Michigan bills allow exceptions for the vaccination requirement for girls whose parents have medical, religious or philosophical issues with having their daughters receive Gardasil. State Sen. Beverly Hammerstrom (R) said that more than 75% of girls who would need to receive the vaccine would be covered by private health insurance or government programs and that the state would have to allocate funding to cover Gardasil through the Michigan Department of Community Health (Kaiser Daily Women's Health Policy Report, 9/14). According to Hammerstron, most employer health plans in the state will cover the vaccine, and girls who are uninsured could be eligible for coverage through the federal Vaccines for Children program. The state Legislature will be in recess until after the November election, so it is not certain when the state Assembly will consider the two bills, the AP/Free Press reports (AP/Detroit Free Press, 9/20).














"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . ??? 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.


View drug information on Gardasil.

Low-Income, Minority Women in Florida Increasingly Avoiding Mammograms Because of Cost

New studies have found that thousands of Florida women, particularly low-income blacks and Hispanics without health insurance, are not receiving mammograms because they cannot afford to pay for screenings, the... South Florida Sun-Sentinel reports. According to the Sun-Sentinel, "[h]igh out-of-pocket medical costs, low Medicaid reimbursements, long wait times at radiology centers and a shortage of doctors conducting the exams" are making the annual breast exams "off limits" to women in Florida who do not have traditional health insurance. In Florida, 21.2% of non elderly residents are uninsured, compared with 17.5% nationwide, according to the Kaiser Family Foundation's statehealthfacts. A series of studies conducted by a committee of health experts for the state Legislature found that 2,500 of the 13,000 Florida women who are diagnosed with breast cancer annually will die from the disease. The studies found that women had to wait an average of 28 days or longer to get tested in 17 of 121 centers that perform breast exams in Broward, Palm Beach and Miami-Dade counties. At 67 cancer-testing sites Orlando, Fla., 40% of women had to wait about a month or more to be screened, the study found. Breast cancer awareness groups, such as the Susan G. Komen Foundation, say long waiting periods are one of main reasons why women avoid testing. To address the issue, several Republican state lawmakers have proposed bills that would limit lawsuit judgments against radiologists by placing a $150,000 cap per claimant on noneconomic damages for negligence in mammogram screening or $300,000 for all claimants. One bill (SB 2470), sponsored by state Sen. Evelyn Lynn (R), also would "toughen the burden of proof in medical liability lawsuits involving breast cancer," the Sun-Sentinel reports. However, attorneys and other lawmakers say that increasing Medicaid reimbursements for screenings will do more to encourage breast cancer screening. Currently, 21% of radiology centers in Florida do not accept Medicaid, and only 4% of women who are Medicaid beneficiaries receive mammograms, according to committee member Betsey Herd (Hollis, South Florida Sun-Sentinel, 3/15).


"Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Stem Cells Found In Amniotic Fluid Appear To Offer Research Benefits, Study Says

Stem cells derived from human amniotic fluid appear to offer many of the benefits of embryonic stem cells -- including the ability to grow into brain, muscle, bone and other tissues -- according to a study published in the Jan. 7 online edition on the journal Nature Biotechnology, the Washington Post reports. For the study, researchers from the Institute for Regenerative Medicine at Wake Forest University and Children's Hospital Boston found that amniotic cells in the laboratory can grow into all of the major types of cells, dividing at the rate of once every 36 hours. Researchers coaxed amniotic fluid stem cells to develop into brain cells and injected them into the skulls of mice with diseased brains. The stem cells replaced the diseased areas and appeared to create new connections with surrounding healthy neurons, the researchers reported. Researchers also coaxed amniotic fluid stem cells to become bone cells and implanted them in a mouse. The study found the stem cells calcified and turned into dense, healthy bone. The researchers also coaxed amniotic fluid stem cells to develop into muscle, fat, blood vessel and liver cells. Stem cells extracted from amniotic fluid can be isolated starting at 10 weeks' gestation from fluid taken during tests performed to identify birth defects, according to the study. The stem cells, even after more than two years in the laboratory, did not show signs of aging or of having the potential to grow into tumors, the study found. Amniotic stem cells can be frozen for later use, the Post reports.

Reaction
According to the Post, amniotic fluid stem cells are "adding credence to an emerging consensus among experts that the popular distinction" between human embryonic stem cells and adult stem cells is "artificial" and that there is a "continuum of stem cell types" (Weiss, Washington Post, 1/8). Amniotic fluid stem cells are a "different kind of stem cell" that is "not as early as a human embryonic stem cell, and it's not as late as the adult stem cells," Anthony Atala, senior author of the study and director of the Institute for Regenerative Medicine at Wake Forest, said, adding, "So far, we've been successful with every cell type we've attempted to produce from these stem cells" (Kaplan, Los Angeles Times, 1/8). Atala said that if 100,000 women donated their amniotic stem cells to a cell bank, it would provide enough cells for "99% of the U.S. population with a perfect match for genetic transplantation" (Weise, USA Today, 1/8). He added that the stem cells can be found not only in amniotic fluid but also in the placenta, which is discarded after birth (Washington Post, 1/8). Richard Doerflinger, deputy director of the U.S. Conference of Catholic Bishops Secretariat for Pro-Life Activities, said that the study "is one in a line of studies showing very versatile stem cells can be obtained from a number of different products after live birth -- amniotic membrane, amniotic fluid, cord blood, placenta, even umbilical cord tissue," adding, "There is no reason why the amniotic fluid couldn't be obtained, raising no moral problem whatever" (Hall, San Francisco Chronicle, 11/8). Atala said it is unclear how many different cell types can be produced from amniotic stem cells, and researchers said that it will be several years before preliminary tests can be performed on patients, the AP/Houston Chronicle reports (Elias, AP/Houston Chronicle, 1/7). "[Amniotic fluid stem cells] can clearly generate a broad range of important cell types, but they may not do as many tricks as embryonic stem cells," Robert Lanza, head of scientific development for Advanced Cell Technology, said (Los Angeles Times, 1/8).














The study is available online.

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.