MedicalResearch.com Interview with:
Marc Brisson
Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease
Associate Professor, Université Laval
Medical Research: What is the background for this study? What are the main findings?
Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions. Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs.
In countries with high female vaccination coverage (<50%), our main findings indicate:
MedicalResearch.com Interview with:
Elmar A. Joura, M.D
Gynecologist
University of Vienna
MedicalResearch: What are the main findings of this study?
Dr. Joura: This study demonstrates that the new ninevalent HPV vaccine induces a good immunogenicity against HPV 6/11/16/18 and gives a 97% protection against disease caused by HPV 31/33/45/52/58. This has a potential of a 90% reduction of cervical cancer and other HPV related cancers and a similar protection against genital warts. The full benefit is seen in persons without current HPV infection, this reinforces early vaccination against HPV. The safety profile was favourable.
Dr Matthew R Moore, MD
National Center for Immunization and Respiratory Diseases,
Centers for Disease Control and Prevention, Atlanta, GA, USA
MedicalResearch: What is the background for this study?
Dr. Moore: Since introduction, pneumococcal conjugate vaccines have resulted in dramatic decreases in the number of cases of invasive pneumococcal disease in both children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine infant immunization program in the United States in 2000. It was recommended for infants using a 4-dose schedule: 2, 4, 6, and 12 through 15 months of age. Studies showed that PCV7 was highly effective in preventing invasive pneumococcal disease. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 using the same 4-dose schedule. PCV13 is similar to PCV7, but includes protection against six additional serotypes of Streptococcus pneumoniae. There are more than 90 serotypes of pneumococcal bacteria.
Streptococcus pneumoniae, or pneumococcus, is a major cause of illness and death globally. Pneumococcus can cause many types of illness that ranging from mild to life-threatening, including pneumonia, ear and sinus infections, meningitis, and bacteremia. Some of these infections are considered invasive because they invade parts of the body that are normally free from bacteria. Invasive pneumococcal disease, including meningitis and bacteremia, is often severe and can be deadly.
MedicalResearch: What are the main findings?
Dr. Moore: Invasive pneumococcal disease decreased substantially in the first 3 years after PCV13 was introduced into the U.S. infant immunization schedule. By June 2013, more than 30,000 cases of invasive pneumococcal disease and 3,000 deaths are estimated to have been prevented in the United States due to PCV13. Children under the age of five, which is the age group that actually received the vaccine, experienced the greatest and quickest benefit from PCV13. For example, the overall number of cases of invasive pneumococcal disease decreased by 64% in this age group between 2010 and 2013. Significant decreases were seen as early as six months after the immunization recommendation was made.
Adults, who were not targeted for vaccination, also experienced health benefits from PCV13 introduction. For example, the overall number of cases of invasive pneumococcal disease decreased by 32% for adults aged 18 to 49 years, while adults 65 and older experienced a more modest 12% decrease. These reductions are further evidence that both PCV7 and PCV13 reduce the spread of pneumococcus, which is why vaccinating children leads to disease reductions in adults.
For both children and adults, the greatest reductions were seen in the number of cases of invasive pneumococcal disease that were caused by serotypes that are covered by PCV13 but not PCV7 (serotypes 19A and 7F specifically).
MedicalResearch.com Interview with:
Gustavo Dayan, MD
Director, Clinical Development
Sanofi Pasteur Discovery Drive
Swiftwater, PA 18370
Medical Research: What is the background for this study? What are the main findings?
Dr. Dayan: This is the first dengue vaccine efficacy trial conducted in Latin America. The trial met its primary objective showing an efficacy of 60.8% against symptomatic VCD (virologically confirmed dengue) after a 3-dose vaccination schedule. Serotype-specific efficacy was also demonstrated against all four serotypes. Furthermore, the dengue vaccine candidate effectively reduced hospitalization due to dengue by 80.3% and severe dengue disease by 95.5% over the 25-month study period.
MedicalResearch.com Interview with:
Dr. Robert S. DiPaola
Director, Rutgers Cancer Institute of New Jersey
New Brunswick, NJ 08901
Medical Research: What is the background for this study? What are the main findings?
Dr. DiPaola: Despite significant recent improvements in the treatment of advanced castration-resistant prostate cancer, there remains a need for a standard therapy for those patients who have an early relapse with PSA progression after local therapy. Immune therapy with poxvirus vaccines are optimal, because they can induce potent immune responses by mimicking natural infection, have great flexibility regarding antigen composition and are easily administered.
ECOG-ACRIN Cancer Research Group investigators conducted a Phase II clinical trial examining adult patients from member institutions with advanced prostate cancer (as evidenced by two rising prostate-specific antigen or PSA values and no visible metastasis) who had prior surgery or radiation. We explored two different experimental treatment options.
In step one, patients were treated with PROSTVAC-V/TRICOM and PROSTVAC-F/TRICOM. PROSTVAC-V is derived from a vaccinia virus that was used for many years to vaccinate against smallpox. This virus is modified to produce a PSA protein that helps focus the body’s immune response to the PSA in the prostate tumor. In addition, it is modified to produce three other proteins that help increase an immune cell’s ability to destroy its target (TRICOM). PROSTVAC-F is made from the fowlpox virus, which is found in birds and not known to cause any human disease. It contains the same genetic material as PROSTAC-V, but is given multiple times to further boost the body’s immune system.
Patients in the study were given one cycle of PROSTVAC-V/TRICOM followed by PROSTVAC-F/TRICOM for subsequent cycles in combination with a drug known as GM-CSF. GM-CSF is a protein normally made by the body to increase the amount of certain white blood cells and make them more active. When in drug form, it is used to boost the body’s immune system to fight off disease. After six months from first treatment, 25 of 40 eligible patients (63 percent) were found to have no disease progression and experienced minimal toxicity. The rate of rise of PSA also decreased. The second part of the study included the addition of hormone therapy (androgen ablation) to the PROSTVAC-VF/TRICOM combination. In the 27 patients eligible for this step, 20 patients (74 percent) experienced a significant response at seven months.
MedicalResearch.com Interview with:
Anders Hviid, M.Sc., Dr.Med.Sci.
Senior Investigator, Statens Serum Institut
Medical Research: What is the background for this study?
Response: After the widespread introduction of HPV vaccination of adolescent girls, a number of safety concerns have emerged. In this case, demyelinating diseases, including multiple sclerosis, occurring after HPV vaccination has been reported in social media, news media and medical journals.
Medical Research: What are the main findings?
Response: In a study of almost 4 million Danish and Swedish women, we found no support for an increased risk of multiple sclerosis or other demyelinating diseases following HPV vaccination.
MedicalResearch.com Interview with:
Melissa Stockwell, MD, MPH, FAAP
Florence Irving Assistant Professor of Pediatrics and Population and Family Health, Columbia University - College of Physicians & Surgeons and Mailman School of Public Health
Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac);
Co-Director, Primary Care Clinician Research Fellowship in Community Health
Medical Research: What is the background for this study? What are the main findings?
Response: Influenza can be a very serious disease and is more than just a bad cold. Some children who are 6 months through 8 years need two doses of the influenza vaccine in a season depending on if and when they received previous influenza vaccine doses. We know that only about half of these families who want to vaccinate their children against the flu and get the first dose, come back to get the second dose.
MedicalResearch.com Interview with:
Thomas Wisniewski MD
Lulu P. and David J. Levidow Professor of Neurology
Professor; Director Aging and Dementia
New York University School of Medicine
Dept. of Neurology, Psychiatry and Pathology
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Wisniewski: Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. This is a relatively new prion disease that has many similarities to bovine spongiform encephalopathy which spread to humans to produce new variant Creutzfeldt-Jakob disease. Chronic wasting disease is the most infectious prion disease to date; having the potential to spread by aerosol. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk.
MedicalResearch.com Interview with:
Adrian Egli, MD PhD Research Group leader
Infection Biology Laboratory
Department of Biomedicine
University of Basel and University Hospital Basel
Basel, Switzerland
Medical Research: What is the background for this study? What are the main findings?
Dr. Egli: Infections with influenza viruses are associated with a high morbidity and mortality. In particular, people with a weak immune system are at danger for more severe complications. This includes elderly people, pregnant women, patients after transplantation, patients with HIV infection, chronic diseases such as diabetes and many more. In these high-risk groups, annual vaccination is clearly recommended.
However, due to the immunsuppressive condition the immune response to the influenza vaccine is often reduced. The seroconversion rate - a 4-fold antibody titer increase upon vaccination - is one of the key markers for a successful vaccination. In young adults the seroconversion rate is normally >85%; however, in patients with immunosuppression, this can be lower than 40%. Improving vaccine efficacy is one of the key focuses of my research group. We try to understand, how to improve vaccines and better protect the people at the highest risks for influenza-associated complications.
In this study, we could show that an important cytokine, called Interferon lambda, is clearly associated with the vaccine induced antibody response upon influenza vaccination. We could show that genetic polymorphisms, in one of the Interferon lambda gene family (IFNL3), are modulating the expression of this gene. This strongly affects the cross talk between the innate and adaptive immune response in the context of vaccination. We observed that, the more Interferon lambda is present, the lower the antibody response is. People with a lower expression of Interferon lambda had a significant higher response to the vaccine. Therefore, we developed substances to block the effect of Interferon lambda. We could show in vitro, that due to the Interferon lambda blockade, the antibody production was improved.
MedicalResearch.com Interview with:
Leah M. Smith PhD
Department of Epidemiology, Biostatistics, and Occupational Health (Smith, Kaufman, Strumpf)
McGill University, Montréal, Quebec
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: The human papillomavirus (HPV) vaccine protects against types of HPV that cause cervical cancer and anogenital warts. The vaccine first became available in 2006. Since then, it has faced a great deal of controversy surrounding, in part, some of the unanswered questions about the real-world effects of the vaccine, especially on the young girls targeted for immunization. One issue that has received a great deal of public attention has been the concern that HPV vaccination might give girls a false sense of protection against all sexually transmitted infections that might lead them to be more sexually active than they would otherwise. As a result, some parents have been reluctant to have their daughters vaccinated. It is also reason why some religious groups have spoken out against the vaccine. This question is further important from a public health perspective because increases in risky sexual behaviour would inevitably also lead to increases in teen pregnancy and sexually transmitted infections (excluding anogenital warts), which would of course undermine the potential health benefits of the vaccine.
In this study, we directly addressed the question of whether HPV vaccination has led to increases in pregnancy and non-HPV-related sexually transmitted infections (both of which are proxies for risky sexual behaviour) among adolescent girls.
In our study of over 260,000 girls, we did not find any evidence that the HPV vaccine had a negative impact on these outcomes.
MedicalResearch.com Interview with:
Dr. Michael Yeaman Ph.D.
Professor of Medicine, Infectious Disease Specialist
Chief, Division of Molecular Medicine
David Geffen School of Medicine at UCLA
Los Angeles Biomedical Research Institute
Harbor-UCLA Medical Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Yeaman: In the U.S. and around the globe, skin and soft tissue infections caused by
methicillin-resistant Staphylococcus aureus (MRSA) continue to endanger the
health and lives of patients and otherwise healthy individuals. Treatment is
difficult because MRSA is resistant to many antibiotics, and the infections
can recur, placing family members and other close contacts at risk of
infection.
Infectious disease specialists at the Los Angeles Biomedical Research
Institute at Harbor-UCLA Medical Center (LA BioMed) tested a new
investigational vaccine, NDV-3, and found it holds new hope for preventing
or reducing the severity of infections caused by the "superbug" MRSA.
In the study, which was published Dec. 8 in the Proceedings of the National
Academy of Sciences USA, the researchers reported that NDV-3, employing the
recombinant protein Als3, can mobilize the immune system to fight off MRSA
skin infections in an experimental model. The researchers found the vaccine
works by enhancing molecular and cellular immune defenses of the skin in
response to MRSA and other S. aureus bacteria in disease models.
This is the first published study to demonstrate the effectiveness of a
cross-kingdom recombinant vaccine against MRSA skin infections. NDV-3 is
unique as it is the first vaccine to demonstrate it can be effective in
protecting against infections caused by both S. aureus and the fungus
Candida albicans. NDV-3 represents a novel approach to vaccine design that
pioneers an approach termed convergent immunity.
MedicalResearch.com Interview with:
Dr. Raquel Qualls-Hampton MD, MS
Assistant Professor
University of North Texas Health Science Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Qualls-Hampton: There are currently two vaccines approved by the Food and Drug Administration (FDA)—Gardasil for males and Gardasil and Cervix for females – that protect against the human papilloma virus (HPV). These vaccines are recommended by the ACIP for females ages 9 to 26 years and males ages 9 to 21 years. Both vaccines protect males and females against some of the most common types of HPV. HPV vaccines are administered in three doses over six months and are considered safe and effective. However, the promise of these vaccines is going unfulfilled as initiation and completion rates for the three doses are suboptimal among females and males.
Nationally, although HPV vaccination initiation coverage is increasing, overall vaccine completion rates are at suboptimal levels and below the U.S. Department of Health and Human Services’ Healthy People 2020 initiative target of 80%. Thus, many states are turning to legislative interventions in efforts to increase initiation and completion rates. This study examines HPV vaccination legislative initiatives and their impact, specifically in estimating state legislation’s effects on HPV vaccine initiation, completion and patient care provider recommendations by gender.
MedicalResearch.com Interview
Elyse O. Kharbanda MD MPH
HealthPartners Medical and Dental Group
Medical Research: What is the background for this study? What are the main findings?
Dr. Kharbanda: In 2010, due to a pertussis outbreak and neonatal deaths, the California Department of Public Health recommended that the Tdap vaccine be administered during pregnancy. Tdap is now recommended by the Advisory Committee on Immunization Practices (ACIP) for all pregnant women during each pregnancy. We wanted to assess the impact of this recommendation.
The main findings were that Tdap vaccination during pregnancy was not associated with increased risk for hypertensive disorders of pregnancy, preterm birth, or having a baby who is small for his or her gestational age.
The study found a small increased risk for being diagnosed with chorioamnionitis, an inflammation of the fetal membranes caused by bacterial infection. These findings should be interpreted with caution as the magnitude of the risk was small. In addition, there was no associated risk for preterm birth, which often occurs as a result of chorioamnionitis. Furthermore, among the subset of women with a chorioamnionitis diagnosis whose charts were reviewed, many did not have a clinical picture that was clearly consistent with chorioamnionitis.
Marie R Griffin MD MPH
Director, Vanderbilt MPH Program
Department of Health Policy Vanderbilt University Medical Center
Nashville TN 37212
Medical Research: What is the background for this study? What are the main findings?
Dr. Griffin: In Tennessee, the introduction in 2010 of a new pneumococcal vaccine for infants and young children was associated with a 27 percent decline in pneumonia hospital admissions across the state among children under age 2. The recent decline in Tennessee comes on top of an earlier 43 percent decline across the United States associated with the introduction in 2000 of the first pneumococcal vaccine for children under 2 years of age.
MedicalResearch.com Interview with:
Prof. Clive Maurice Gray
Division of Immunology, Institute of Infectious Diseases and Molecular Medicine,National Health Laboratory Services
University of Cape Town, Cape Town, South Africa
Medical Research: What is the background for this report? What are the main findings?
Prof. Gray: This report is a response on behalf to the International Union of Immunology Societies (IUIS) and is designed to focus a message from the global immunology community to those who are making vaccines and therapies implementing clinical trials and very importantly on Governments and funding bodies. Time is not our side and that vaccine efforts need to be expedited and that production of therapeutics needs to be ramped up. Due to the fact that many people in West Africa are dying, we wish to convey a strong message that to curb this outbreak, therapies and especially vaccines must be rolled out as soon as possible.
Louise-Anne McNutt, PhD
Associate Director, Institute for Health and the Environment
University at Albany, State University of New York
Jessica Nadeau, PhD
Epidemiologist, University at Albany, State University of New York
Medical Research: What are the main findings of the study?
Response: The study found that about 25% of infants consistently deviated from the routine vaccine schedule recommended by the American Academy of Pediatrics (AAP). Alterations included either consistently refusing a recommended vaccine or reducing the number of vaccines given at each visit.
These deviations are generally associated with intent to use an alternative vaccination schedule.
Infants who did not follow the AAP recommended schedule were more likely to be unprotected against vaccine preventable diseases for a longer period of time. Only 1 in10 infants vaccinated on an alternative schedule were up-to-date at 9 months of age.
MedicalResearch.com Interview with
Scott E. Hensley, Ph.D.
Assistant Professor, The Wistar Institute
Philadelphia, PA 19104
Medical Research: What are the main findings of the study?
Dr. Hensley: We found that H1N1 viruses recently acquired a mutation that abrogates binding of influenza antibodies that are present in a large number of middle-aged adults. We propose that this mutation lead to increased disease among middle-aged adults during the 2013-2014 influenza season.
MedicalResearch.com Interview with:
Dr. Susanne Huijts
Research Physician at UMCU Julius Center for Health Sciences Pulmonary resident, UMC Utrecht Center
Utrecht, Netherlands
Medical Research: What are the main findings of the study?
Dr. Huijts: The CAPiTA trial evaluated the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults of 65 years and older. In the per protocol analysis vaccine efficacy of 45.6% was demonstrated for the first episode vaccine type (VT) pneumococcal community acquired pneumonia (CAP); 45.0% for the first episode of non-bacteremic/ non-invasive (NB/NI) VT-CAP, and 75.0% for the first episode of VT-invasive pneumococcal disease.
MedicalResearch.com Interview with:
Robert B Belshe, MD
Division of Infectious Diseases, Allergy & Immunology
Saint Louis University School of Medicine
Medical Research: What are the main findings of the study?
Response: A vaccine that protects against an old strain of avian flu primes the immune system to mount a rapid response when a vaccine designed to protect against a related but different and new strain of avian flu is given a year later, according to Saint Louis University research findings reported in JAMA.
In addition, when combined with an adjuvant, which is a chemical that stimulates the immune system to produce more antibodies, a lower dose of the new avian flu vaccine worked better in triggering an immune response than a stronger dose without adjuvant. That means the amount of vaccine against a new strain of bird flu can be stretched to protect more people if an adjuvant is added.
Both findings represent important strategies researchers can continue to study to fight new strains of bird flu that people previously have not been exposed to, and consequently can rapidly turn into a pandemic outbreak and public health emergency, said Robert Belshe, M.D., professor of infectious diseases, allergy and immunology at Saint Louis University and the lead author of the article, which appeared in the Oct. 8, 2014 issue of JAMA.
MedicalResearch.com Interview with:
Elmar A. Joura, MD
Department of Gynaecology and Obstetrics
Medical University of Vienna, Comprehensive Cancer Center
Vienna, Austria
Medical Research: What are the main findings of the study?
Dr. Joura: The upcoming ninevalent vaccine has the potential to prevent 85% of the cervical precancers and surgeries such as LEEP (conization)
MedicalResearch.com interview with:
Dr. Shannon MacDonald PhD
Department of Pediatrics, University of Calgary, Calgary and
Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada
Medical Research: What are the main findings of the study?
Dr. MacDonald: We found that vitamin K was refused by only a very small number of parents in our study population (0.3%) but that the number appears to be increasing (almost doubling in the past 7 years). The parents that refused vitamin K for their child were more likely to be those that delivered at home and/or with a midwife. We also found that parents who refused vitamin K for their child were also much more likely to go on to refuse all vaccinations by 15 months of age.