Safety and immunogenicity of two doses of the HPV-16/18 AS04 adjuvanted vaccine Cervarix

March 28, 2014

A recent study in the journal Human Vaccines & Immunotherapeutics, showed that two doses of the HPV-16/18 AS04-adjuvanted vaccine Cervarix (GlaxoSmithKline) are non-inferior to three-doses in the current schedule.

Since high coverage and compliance rates can be difficult to achieve with the current three-dose HPV vaccineregimen, several studies have looked at the possibility of reducing the number of doses. Proof-of-principle that a two-dose schedule can provide sufficient protection against cervical cancer came initially from a study performed in Costa Rica in 2011. Since then, several countries have considered switching to a two-dose schedule or have already done so. The European Commission recently granted marketing authorization for Cervarix as a two-dose schedule for girls aged 9-14 years, and outside of the EU, the Cervarix two-dose schedule is approved in more than ten countries, including Panama, Guatemala, Honduras, El Salvador, Haiti, Suriname, Chile, Guyana, Nigeria, Ghana, Pakistan, and Bangladesh.

The randomized, partially-blinded Phase I/II clinical trial evaluated the immunogenicity and safety of two doses of the licensed formulation of Cervarix (20 µg each of HPV-16 and HPV-18 L1 VLPs, ,20/20') or an alternative formulation (40 µg of each HPV-16 and HPV-18 VLPs; ,40/40') in different age groups, compared with the standard three-dose schedule of the licensed formulation. Healthy females (age stratified: 9-14, 15-19, 20-25 years) were randomized to receive two doses of vaccine at months 0 and 6, or three doses of the vaccine at months 0, 1, and 6.

The trial was initiated in 2007 and conducted at 21 centers in Canada and Germany. Results from 24 months of analysis were previously published in HV&I, and the current study presents results from 48 months of analysis. Since the two-dose 40/40 formulation gave no added benefit, the current study focused on data for the two-dose 20/20 formulation in girls aged 9-14 years and the standard three-dose 20/20 schedule in women aged 15-19 years.

The researchers reported that all initially seronegative subjects seroconverted for HPV-16 and HPV-18 antibodies and remained seropositive up to 48 months. The kinetics of HPV-16, -18, -31, and -45 antibody responses were similar for both groups, and the HPV-16 and -18 geometric mean antibody titers were substantially higher than titers following natural infection. The vaccine had a clinically acceptable safety profile in both groups. In summary, antibody responses to a two-dose schedule of the licensed vaccine formulation in girls aged 9-14 years appeared comparable to the standard three-dose schedule in women aged 15-19 years for up to four years after first vaccination.

These results show that a two-dose schedule should confer a similar level of protection against HPV infections and subsequent development of cervical lesions and cancer as the current three-dose schedule. A two-dose schedule obviously would be more convenient for physicians and patients, and could help reduce associated costs. The authors think that these benefits could facilitate the implementation of HPV immunization programs in low-income countries, as well as improve the relatively low vaccine coverage and series completion rates observed in some developed countries.

"Compliance has been a major challenge for HPV vaccination. These data reinforce the value of the two-dose schedule and should lead to increased utilization of this , with consequent decreases in morbidity and mortality from ," said Dr. Ronald Ellis, Editor-in-Chief of Human Vaccines & Immunotherapeutics.

Explore further: Three doses of HPV vaccine recommended against genital warts

Related Stories

Three doses of HPV vaccine recommended against genital warts

February 11, 2014
Two doses of vaccine against human papillomavirus (HPV) provide good protection against genital warts, but three doses is better according to an extensive register study by researchers at Karolinska Institutet in Sweden. ...

One dose of HPV vaccine may be enough to prevent cervical cancer

November 4, 2013
Women vaccinated with one dose of a human papillomavirus (HPV) vaccine had antibodies against the viruses that remained stable in their blood for four years, suggesting that a single dose of vaccine may be sufficient to generate ...

Study compares effectiveness of 2 vs. 3 doses of HPV vaccine for girls and young women

April 30, 2013
With the number of doses and cost of human papillomavirus (HPV) vaccines a barrier to global implementation, researchers have found that girls who received two doses of HPV vaccine had immune responses to HPV-16 and HPV-18 ...

President's panel calls for more girls, boys to get HPV vaccine

February 10, 2014
(HealthDay)—Too few American girls and boys are getting vaccinated against the cancer-causing human papillomavirus (HPV), the President's Cancer Panel reported Monday.

Lengthening dosing schedule of HPV vaccine may provide effective option for expanding use of vaccine

April 12, 2011
Administration of human papillomavirus (HPV) vaccine doses over a longer period of time to adolescent girls in Vietnam resulted in antibody concentration levels that were comparable to the standard vaccine schedule, according ...

Fewer than three doses of cervical cancer vaccine effective

September 9, 2011
Fewer than three doses of the human papillomavirus (HPV) vaccine Cervarix may be just as effective as the standard three-dose regimen when it comes to preventive measures against cervical cancer, according to a new study ...

Recommended for you

Genetic immune deficiency could hold key to severe childhood infections

July 18, 2017
A gene mutation making young children extremely vulnerable to common viruses may represent a new type of immunodeficiency, according to a University of Queensland researcher.

What are the best ways to diagnose and manage asthma?

July 18, 2017
What are the best ways to diagnose and manage asthma in adults? This can be tricky because asthma can stem from several causes and treatment often depends on what is triggering the asthma.

Large multi-ethnic study identifies many new genetic markers for lupus

July 17, 2017
Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus.

Study finds molecular explanation for struggles of obese asthmatics

July 17, 2017
A large, bouquet-shaped molecule called surfactant protein A, or SP-A, may explain why obese asthma patients have harder-to-treat symptoms than their lean and overweight counterparts, according to a new study led by scientists ...

Team identifies potential cause for lupus

July 14, 2017
Leading rheumatologist and Feinstein Institute for Medical Research Professor Betty Diamond, MD, may have identified a protein as a cause for the adverse reaction of the immune system in patients suffering from lupus. A better ...

Immunosuppression underlies resistance to anti-angiogenic therapy

July 14, 2017
A Massachusetts General Hospital (MGH) research team has identified a novel mechanism behind resistance to angiogenesis inhibitors - drugs that fight cancer by suppressing the formation of new blood vessels. In their report ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.