Table of Contents

Volume 6, Issue 7

  July 2010

  Pages 523 - 607

View covers archive

 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva Riedmann
Page 523
http://dx.doi.org/10.4161/hv.6.7.12812
PDF




NEWS, POLICY AND PROFILES

Open Access Article

On-time shots are safe for babies

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12820
PDF

Open Access Article

PROVENGE shows few side effects

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12821
PDF

Open Access Article

Brain cancer vaccine looks promising in small trial

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12822
PDF

Open Access Article

Only one-third of girls receive HPV vaccine

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12823
PDF

Open Access Article

Therapeutic CMV vaccine: Promising Phase II trial

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12824
PDF

Open Access Article

Linking Smallpox eradication to spread of HIV

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12825
PDF

Open Access Article

Future pandemic vaccines may face suspicion

Eva Riedmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12826
PDF

Open Access Article

Questions for biotechs

Martin Bachmann
Pages 524 - 527
http://dx.doi.org/10.4161/hv.6.7.12827
PDF




PORTAIT OF A LEADING VACCINOLOGIST

Open Access Article

A normal life in science

Beth-Ann Griswold Coller
Pages 528 - 531
http://dx.doi.org/10.4161/hv.6.7.12344
PDF




REVIEWS

Open Access Article

Performance of rotavirus vaccines in developed and developing countries

Victoria Jiang, Baoming Jiang, Jacqueline Tate, Umesh D. Parashar and Manish M. Patel
Pages 532 - 542
http://dx.doi.org/10.4161/hv.6.7.11278
Abstract | PDF

The World Health Organization estimates that rotavirus diarrhea results in approximately half a million deaths and approximately 2.4 million hospitalizations in developing countries each year. Two live oral rotavirus vaccines, RotaTeq© (RV5; Merck) and Rotarix© (RV1; GlaxoSmithKline) with good efficacy against severe rotavirus disease and a reassuring safety profile could substantially impact the burden of rotavirus disease. In April 2009, WHO provided a recommendation for global introduction of these vaccines in national immunization programs of developing countries worldwide. In this article, we review published data on previous candidate rotavirus vaccines and vaccines in current use, with emphasis on their performance in developed versus developing countries. In developed countries, both first and second generation rotavirus vaccines have demonstrated high efficacy against severe rotavirus disease (pooled efficacy = 73% and 85%, respectively). In developing countries, small early trials for the first generation vaccines failed to provide protection against rotavirus disease (pooled efficacy = 20%), however, trials of the second generation vaccines yielded substantial improvements in efficacy in developing countries (pooled efficacy of 51%), leading to a global recommendation for rotavirus vaccine introduction by WHO. Future efforts for these vaccines should focus on optimizing the efficacy and delivery of these vaccines in challenging target populations of Asia and Africa with the greatest burden of severe rotavirus disease.

Open Access Article

Development of improved vaccines against whooping cough: Current status

Ibrahim Marzouqi, Peter Richmond, Scott Fry, John Wetherall and Trilochan Mukkur
Pages 543 - 553
http://dx.doi.org/10.4161/hv.6.7.11413
Abstract | PDF

Prior to the introduction of killed whole cell pertussis vaccine [wP] in the 1940s, whooping cough was a major cause of infant death worldwide. Widespread vaccination of children with this vaccine caused a significant reduction in mortality. However in the 1990s and now more recently, there has been a resurgence of pertussis in several countries even in populations previously vaccinated with an acellular pertussis vaccine [aP]. In this review, we describe the epidemiology of whooping cough, the vast array of virulence factors produced by this pathogen potentially contributing to the resurgence of pertussis even in previously vaccinated populations of infants and children, history of whooping cough prophylaxis, possible mechanisms of immunity, lack of availability of a suitable non-toxic adjuvant capable of inducing both arms of the immune response, and the current status of development of improved vaccines with potential to induce longer-lasting protection, than is currently possible with the wP or aP vaccines, against whooping cough.




RESEARCH PAPERS

Open Access Article

Repeated administration of a reduced-antigen-content diphtheria-tetanus-acellular pertussis and poliomyelitis vaccine (dTpa-IPV; Boostrix™ IPV)

Markus Knuf, Volker Vetter, Froilan Celzo, Gunasekaran Ramakrishnan , Olivier Van Der Meeren and Jeanne M Jacquet
Pages 554 - 561
http://dx.doi.org/10.4161/hv.6.7.11760
Abstract | PDF

Background: The rising incidence of pertussis amongst adults and adolescents in industrialised countries could be reduced by replacing tetanus and diphtheria (Td) boosters with reduced-antigen-content dT-acellular pertussis (dTpa) vaccines. Repeated administration of a dTpa-IPV (dTpa-inactivated poliomyelitis; Boostrix™ Polio, GlaxoSmithKline) booster to adolescents, 5 years after their previous dose was evaluated. Methods: 415 subjects (mean age 11.4 years) who had received either dTpa-IPV or dTpa + IPV at age 4-8 years, all received one dose of dTpa-IPV in this open, phase IV trial. Blood samples were taken before and one-month post-vaccination. Antibody concentrations against D, T, pertussis toxoid (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and polio antigens were determined. Reactogenicity and safety was assessed. Results: Before the second dTpa-IPV booster, the percentage of subjects who were seroprotected/seropositive was: 98.2% (D); 98.5% (T); 40.6% (PT); 99.7% (FHA); 97.0% (PRN); 98.8% (anti-polio 1); 99.7% (anti-polio 2); 97.0% (anti-polio 3). One-month after the second dTpa-IPV dose, all subjects were seroprotected against D, T and polio and anti-pertussis booster responses (seroconversion or ≥2-fold increase) were seen in 93.3% (PT), 93.4% (FHA) and 95.2% (PRN) of subjects. During 4-day follow-up, 4.1% subjects recorded grade 3 pain; 4.6% and 3.6% recorded redness or swelling >50mm, respectively. No serious adverse events were recorded. The incidence of symptoms was not higher than after the previous booster. Conclusions: A second dTpa-IPV booster was highly immunogenic and well tolerated in this population of adolescents, supporting the repeated administration of Boostrix™ Polio. This study is registered at www.clinicaltrials.gov NCT00635128.

Open Access Article

Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route: Results of a metaanalysis

Mysore K. Sudarshan, Bilagumba Gangaboraiah, Haradanahalli S. Ravish and Doddabele H. Ashwath Narayana
Pages 562 - 565
http://dx.doi.org/10.4161/hv.6.7.11934
Abstract | PDF

The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986 - 2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India & Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) & human diploid cell vaccine (MIRV, France).The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1ml per site. The vaccines were administered to 1011subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson’s correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route. (p> 0.230 and p>0.568)

Open Access Article

Predictors of influenza vaccination uptake among adults with a history of heart attack

Rodrigo Jiménez-García , Valentín Hernández-Barrera , Ana Lopez de Andres , Isabel Jimenez-Trujillo, Jesus Esteban, Angel Gil and Pilar Carrasco-Garrido
Pages 566 - 571
http://dx.doi.org/10.4161/hv.6.7.11884
Abstract | PDF

Background: Influenza vaccination can reduce morbidity and mortality caused by cardiovascular diseases. This study sought to evaluate influenza vaccination coverage among adults with a history of heart attack and to determine which variables were associated with vaccine uptake. Design: A descriptive study was conducted using individual data from adults aged ≥ 40 years included in the year 2006/7 Spanish Health Survey and comparing subjects with a history of heart attack with those who had not suffered this event. Methods: The number of participants surveyed was 20,060. Subjects were classified as heart attack sufferers if they answered affirmatively to the question: "Has your doctor told you that you have suffered a heart attack?" To assess influenza vaccination status we considered the response to the question, "Did you have a 'flu shot in the latest campaign?". Independent variables included sociodemographic, health-related, lifestyles and periodic control of cardiovascular risk factors. Results: A total of 716 adults reported having suffered a heart attack. The coverage among sufferers was 67.9% as against 35% for non sufferers. The variables that were significantly associated with a higher likelihood of receiving the vaccine among sufferers were: higher age; male gender, no smoking habit, "Physician visits in the preceding four weeks"; and, "Blood pressure control in the preceding three months". Conclusions: Influenza vaccination coverage among subjects who have suffered a heart attack is below desirable levels. Multiple strategies focused on providers and patients are needed to improve influenza vaccination coverage among these high risk subjects, particularly now with the emerging H1N1 pandemic.

Open Access Article

Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with EasyFourTM in Indian infants administered per EPI schedule: A phase III trial

Mandeep S Dhingra, Raman Rao, Swarnarekha Bhat, Rajan Joshi, Veena Kalra, Harish R. Parikh, S. Narasimha Rao, G. R. Sethi, Nitin Shah and M Muzaffaruddin
Pages 572 - 577
http://dx.doi.org/10.4161/hv.6.7.11817
Abstract | PDF

The study was planned to assess and compared immunogenicity and safety of an indigenous DTPw-Hib combination vaccine (Shan 4) with EasyFour, the available DTwP-Hib vaccine in India. Overall 210 healthy infants, six to eight weeks of age were randomized to receive three doses of either Shan 4 or EasyFour at 6, 10 and 14 weeks of age. Antibodies were analyzed prior to and four to six weeks post third vaccine dose. Solicited and unsolicited local and systemic events in the follow up period after each dose were recorded. Post vaccination 100% of the infants in Shan 4 and EasyFour groups had seroprotective concentrations of Anti PRP-T IgG antibodies, IgG anti-diphtheria toxoid antibodies and IgG anti-tetanus toxoid antibodies. Following third dose of vaccination 86.99% subjects in the Shan 4 group and 73.85% subjects in the EasyFour group seroconverted for anti-pertussis antibody titres. Two Serious Adverse Events (SAEs) were reported during the course of the study, all unrelated to the respective vaccine administered. Most commonly reported adverse events in both the groups were pain at injection site, mild fever (< 103° F) and minor swelling at injection site. The study proved that Shan 4 was safe and immunogenic compared to the available licensed vaccine.

Open Access Article

Safety and immunogenicity of an investigational adjuvanted hepatitis B vaccine (HB-AS02_V) in healthy adults

Jiří Beran, Lenka Hobzova, Veronika Wertzova, Sherine Kuriyakose, Maarten Leyssen, Murielle Surquin and Sophie Houard
Pages 578 - 584
http://dx.doi.org/10.4161/hv.6.7.11883
Abstract | PDF

HB-AS02 is an investigational adjuvanted hepatitis B virus (HBV) vaccine for potential use in patients with renal insufficiency and other immunocompromized individuals. In this Phase III lot-to-lot consistency study, 450 healthy adult volunteers who had not previously been vaccinated against HBV were randomized to one of three production lots of HB-AS02 at 0 and 1 month and followed until one month after the last vaccine dose. Lot-to-lot consistency was established. High seroprotection rates were already achieved after the first vaccine dose (75.9%). All subjects were seroprotected (anti-HBs antibody concentrations ≥10 mIU/ml) after two doses, with all but one subject achieving anti-HBs antibody concentrations ≥100 mIU/ml (99.7%). Geometric mean anti-HBs antibody concentration was 4594.5 mIU/ml. Local and general symptoms were reported after 80.7% and 45.5% of doses, respectively. However, these were mainly of mild or moderate severity and no subject withdrew from the study due to adverse events.

Open Access Article

Efficacy, immunogenicity and stability of a novel intranasal Nanoemulsion-adjuvanted influenza vaccine in a murine model

Tarek Hamouda, Alexander Chepurnov, Nicholas Mank, Jessica Knowlton, Tatiana Chepurnova, Andrzej Myc, Joyce Sutcliffe and James Baker, Jr.
Pages 585 - 594
http://dx.doi.org/10.4161/hv.6.7.11818
Abstract | PDF

Mutations of influenza virus increase concerns of worldwide epidemics resulting from the newly emergent strains. Current influenza vaccines are inefficient and require annual vaccinations. W805EC adjuvant is an oil-in-water emulsion composed of nanodroplets with an average diameter of approximately 400 nm. The nanoemulsion adjuvant has been used successfully to stimulate the immune response when mixed with several other antigens in animal models. In this study, W₈₀5EC nanoemulsion adjuvant activity was evaluated using nasal influenza vaccination in a murine model. Five to twenty percent W₈₀5EC adjuvant was used to inactivate influenza A/Puerto Rico/8/34/05 (H1N1). Mice immunized with the nanoemulsion adjuvanted influenza virus intranasally showed a robust specific humoral immune response as demonstrated using ELISA and HAI assays. Serum HAI titers were more than 104 following two vaccinations. Vaccinated mice were also protected against challenge with an LD₈₀ of live influenza virus. Splenocytes from vaccinated mice were assayed for cytokine production following virus stimulation. The cytokine profile demonstrated a robust cellular immune response with enhanced Th1 and Th17 immunity that provided balanced immunity against both intracellular and extracellular forms of the virus. Additionally, the vaccine preparations showed minimal protein degradation but remained potent when stored at 4ºC for up to three months. This work demonstrates that W805EC nanoemulsion adjuvant can effectively enhance the immunogenicity of influenza hemagglutinin antigen. The nanoemulsion adjuvant can result in antigen sparing and cross-protection. The potential exists for a nasally administered influenza vaccine that may require little or no refrigerated storage.




COMMENTARIES

Open Access Article

Vaccination in a post earthquake crisis

Viroj Wiwanitkit
Pages 595 - 596
http://dx.doi.org/10.4161/hv.6.7.11661
Abstract | PDF

Earthquakes are a kind of natural disaster. Several infectious diseases should be considered important emerging diseases in post-disaster situations and adequate prevention measures should be implemented in these circumstances. For prevention, vaccination is an important infection control method. In this brief article, the author will discuss the importance of vaccination in post-earthquake situation.

Open Access Article

Rift Valley fever virus: An unrecognized emerging threat?

Robert B. Mandell and Ramon Flick
Pages 597 - 601
http://dx.doi.org/10.4161/hv.6.7.11761
Abstract | PDF

Rift Valley fever virus (RVFV) is an arthropod-borne pathogen that often results in severe morbidity and mortality in both humans and livestock. As its geographic range continues to spread, it presents a real threat to naïve populations around the world by accidental introduction (e.g., the result of increased world travel) or a bioterror event. The lack of prophylactic and therapeutic measures, the potential for human-to-human transmission, and the significant threat to livestock associated with RVFV make infection with these pathogens a serious public health concern. Rift Valley fever epizootics and epidemics might rapidly overwhelm the capacities of the public health and veterinary medical communities to provide rapid diagnostic testing, distribution of countermeasures and adequate medical care.

Open Access Article

China’s emerging vaccine industry

Jan Hendriks, Yan Liang and Bing Zeng
Pages 602 - 607
http://dx.doi.org/10.4161/hv.6.7.11933
Abstract | PDF

The Chinese vaccine industry is developing rapidly due to an emerging and large market for current and new vaccines, a large potential for local vaccine manufacturing both in the public and private domain, and a governmental orientation towards national vaccine self-sufficiency. There are currently over 40 companies and institutions manufacturing a large variety of traditional (EPI) and some new vaccines. The innovative development capacity of state vaccine institutions is stimulated by significant government investments. Various Chinese influenza manufacturers were in 2009 among the first worldwide to obtain national license for their pandemic H1N1 flu vaccines. It is of interest to note that private but also governmental entities are committed to raise manufacturing quality standards to reach WHO prequalification. It is expected that WHO prequalification for at least one product from a Chinese manufacturer will have been obtained by 2011. This will open the door to the global market for Chinese vaccines.