Table of Contents

Volume 8, Issue 2

  February 2012

  Pages 147 - 280

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EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva M. Riedmann
Page 147
http://dx.doi.org/10.4161/hv.19649
PDF

Open Access Article

Human Vaccines & Immunotherapeutics awards Top Reviewer of the Year

Eva M. Riedmann
Pages 148 - 150
http://dx.doi.org/10.4161/hv.19657
Abstract | PDF

Human Vaccines & Immunotherapeutics (HV&I, formerly Human Vaccines) recently started its 8th year of publication.

Each month, we publish a mix of high-quality original research and solicited content including timely reviews, commentaries, news, portraits, and much more. HV&I has become well-established in the vaccine community as an important forum for companies, academics, governmental and non-governmental organizations in this field. Our journal’s unique and exclusive focus on vaccines and immunotherapeutics for human use coupled with the rapid turnaround from submission through peer review to acceptance has allowed HV&I to continuously increase its content and progressively improve its standing relative to other journals in the field. 

Obviously, the successful development of HV&I would not have been possible without the many scientists who have served as peer reviewers for HV&I. We want to take this opportunity to thank all our reviewers for their time and commitment. All peer reviewers of 2011 are listed below. 

In particular, we are very pleased to recognize Dr. Arístides Aguilar Betancourt (Centre for Genetic Engineering & Biotechnology, Biomedical Research Branch, Vaccines Division, Havana, Cuba) as Top Reviewer 2011 for Human Vaccines & Immunotherapeutics. On behalf of Landes Bioscience, we want to thank him for his commitment with a special gift.

Previous Awardees were Drs. Brian Greenwood (London School of Hygiene and Tropical Medicine, UK), Brian Ward (McGill University, Montreal, Canada), James Tartaglia (Sanofi-Pasteur, Toronto, Canada), Joel Bozue (USAMRIID Bacteriology, Fort Detrick, MD, USA), and Mark Kane (Consultant, Mercer Island, Seattle, WA, USA).Human Vaccines & Immunotherapeutics (HV&I, formerly Human Vaccines) recently started its 8th year of publication.

Each month, we publish a mix of high-quality original research and solicited content including timely reviews, commentaries, news, portraits, and much more. HV&I has become well-established in the vaccine community as an important forum for companies, academics, governmental and non-governmental organizations in this field. Our journal’s unique and exclusive focus on vaccines and immunotherapeutics for human use coupled with the rapid turnaround from submission through peer review to acceptance has allowed HV&I to continuously increase its content and progressively improve its standing relative to other journals in the field. 

Obviously, the successful development of HV&I would not have been possible without the many scientists who have served as peer reviewers for HV&I. We want to take this opportunity to thank all our reviewers for their time and commitment. All peer reviewers of 2011 are listed below. 

In particular, we are very pleased to recognize Dr. Arístides Aguilar Betancourt (Centre for Genetic Engineering & Biotechnology, Biomedical Research Branch, Vaccines Division, Havana, Cuba) as Top Reviewer 2011 for Human Vaccines & Immunotherapeutics. On behalf of Landes Bioscience, we want to thank him for his commitment with a special gift.

Previous Awardees were Drs. Brian Greenwood (London School of Hygiene and Tropical Medicine, UK), Brian Ward (McGill University, Montreal, Canada), James Tartaglia (Sanofi-Pasteur, Toronto, Canada), Joel Bozue (USAMRIID Bacteriology, Fort Detrick, MD, USA), and Mark Kane (Consultant, Mercer Island, Seattle, WA, USA).




NEWS, POLICY AND PROFILES

Open Access Article

News

Eva M. Riedmann
Pages 151 - 154
http://dx.doi.org/10.4161/hv.19658
Abstract | PDF

FDA approves Prevnar 13 for people ages 50 and older
Search for AIDS vaccine advances
Positive Phase II interim data on AE37 cancer vaccine released
Pfizer and GSK provide more discount vaccines for GAVI
Promising Phase I study on hepatitis C vaccine New candidate vaccine neutralizes all tested strains of malaria parasite
New type of dendritic-cell-based cancer vaccine enters the clinic
Experimental cancer vaccine shrinks tumor in mice




PORTRAIT OF A LEADING VACCINOLOGIST

Building bridges between the public and private sectors

Clement Lewin
Pages 155 - 158
http://dx.doi.org/10.4161/hv.19748
PDF




BOOK REVIEW

Deadly Choices : How the Anti-Vaccine Movement Threatens Us All

Ian Gust
Pages 159 - 160
http://dx.doi.org/10.4161/hv.18371
Abstract | PDF

A review of Paul Offit’s “Deadly Choices: How the Anti-Vaccine Movement Threatens Us All.” Basic Books; New York, NY 2010.




REVIEW

Open Access Article

Safety, immunogenicity and efficacy of pneumococcal conjugate vaccine in HIV-infected individuals

Marta C. Nunes and Shabir A. Madhi
Pages 161 - 173
http://dx.doi.org/10.4161/hv.18432
Abstract | Full Text | PDF

Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults.

 

Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ≥ 25% and if the nadir CD4+ is >15%. Although the efficacy of PCV was lower, the vaccine preventable burden of hospitalization for IPD and clinical pneumonia were 18-fold and 9-fold greater, respectively, in HIV-infected children compared with –uninfected children.

In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV. PCV has also been shown to reduce the risk of recurrent IPD by 74% in HIV-infected adults not on ART, albeit, also with subsequent decline in immunity and protection.




PRODUCT HISTORY

Bexsero: A multicomponent vaccine for prevention of meningococcal disease

Andrew R. Gorringe and Rolando Pajón
Pages 174 - 183
http://dx.doi.org/10.4161/hv.18500
Abstract | Full Text | PDF

Serogroup B meningococcal (MenB) disease remains a serious public health problem for which a cross-protective vaccine effective against a wide range of MenB isolates has not been available. Novartis Vaccines has developed a vaccine for the prevention of MenB disease that contains four antigenic components: factor H binding protein (fHbp), neisserial adhesin A (NadA), Neisseria heparin binding antigen (NHBA) and outer membrane vesicles from a New Zealand epidemic strain (which provides PorA). This vaccine has been submitted for regulatory review in Europe so it is timely to review the design of the vaccine, results to date in clinical studies and the potential strain coverage provided by the vaccine. It is also critical to discuss the key issues for the long-term success of the vaccine which include strain coverage, potential persistence of protection, potential effects on carriage of MenB strains, potential for escape mutants and cost effectiveness.




SHORT REPORT

Evaluation of the establishment of herd immunity in the population by means of serological surveys and vaccination coverage

Pedro Plans-Rubió
Pages 184 - 188
http://dx.doi.org/10.4161/hv.18444
Abstract | Full Text | PDF

The necessary herd immunity blocking the transmission of an infectious agent in the population is established when the prevalence of protected individuals is higher than a critical value, called the herd immunity threshold. The establishment of herd immunity in the population can be determined using the vaccination coverage and seroepidemiological surveys. The vaccination coverage associated with herd immunity (V_c) can be determined from the herd immunity threshold and vaccine effectiveness. This method requires a vaccine-specific effectiveness evaluation, and it can be used only for the herd immunity assessment of vaccinated communities in which the infectious agent is not circulating. The prevalence of positive serological results associated with herd immunity can be determined from the herd immunity threshold, in terms of prevalence of antibodies (p_c) and serological test performance. The herd immunity is established when the prevalence of antibodies is higher than p_c. This method can be used to assess the establishment of herd immunity in different population groups, both when the infectious agent is circulating and when it is not possible to assess vaccine effectiveness. The herd immunity assessment in Catalonia, Spain, showed that the additional vaccination coverage required to establish herd immunity was 3–6% for measles, mump and varicella and 11% poliovirus type III in school children, 17–59% for diphtheria in youth and adults and 25–46% for persussis in school children, youth and adults.




RESEARCH PAPERS

Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid

Aamir Ali, So Jung An, Changfa Cui, Abdul Haque and Rodney Carbis
Pages 189 - 193
http://dx.doi.org/10.4161/hv.18350
Abstract | Full Text | PDF

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization  schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response.

Comparison of antigen expression from plasmid DNA in tumor-free and antigen-expressing tumor-bearing mice

Xin Guan, Makiya Nishikawa, Hisoon Li, Takahashi Rei, Yuki Takahashi and Yoshinobu Takakura
Pages 194 - 200
http://dx.doi.org/10.4161/hv.18370
Abstract | Full Text | PDF

Reduced antigen expression after DNA vaccination could be a factor that limits its therapeutic effects in antigen-expressing tumor-bearing hosts. To examine whether the presence of an antigen-positive tumor results in the destroy of antigen-expressing cells, pCMV-OVA plasmid expressing ovalbumin (OVA), a model antigen, was intradermaly injected to tumor-free mice and those bearing an EG7-OVA tumor, which stably expresses OVA. For a quantitative evaluation of the elimination of antigen-expressing cells, a plasmid independently expressing firefly luciferase and OVA (pCMV-Luc/OVA) was injected to mice that had been untreated or administered with pCMV-OVA, and luciferase activity was measured one week after the administration. In both tumor-free and tumor-bearing mice, a pre-injection of pCMV-OVA reduced the luciferase expression from pCMV-OVA/Luc compared with a pre-injection of an empty plasmid, suggesting that an immune response to antigen-expressing cells is induced. In tumor-bearing mice, OVA-specific humoral and cellular immune responses were detected even before the vaccination, but such responses had no significant effects on the luciferase expression from pCMV-OVA/Luc. These results indicate that DNA vaccination can induce antigen-specific immune response even in tumor-bearing mice, although it is not strong enough to reject the tumor burden.

The burden of hospitalizations for anus and penis neoplasm in Spain (1997–2008)

Ruth Gil-Prieto, Pablo Viguera Ester, Alejandro Álvaro-Meca, María San Martín Rodríguez and Angel Gil de Miguel
Pages 201 - 207
http://dx.doi.org/10.4161/hv.18388
Abstract | PDF

An epidemiological retrospective study has been performed to assess the burden of hospitalization by anus and penis neoplasm in the general population in Spain. All hospital discharges and deaths related to anal malign neoplasm and penile malign neoplasm from 1997 to 2008 in Spain were obtained. A total of 19,608 hospital admissions were recorded during the study period: 11,965 were related to anal malign neoplasm (4,992 in women and 6,973 in men) and 7,643 to penis malignant neoplasm. This corresponds to a hospitalization rate of 1.97 (CI 95%: 1.91–2.02) hospitalizations per 100,000 women/ year, 2.84 (CI 95%: 2.77–2.91) hospitalizations per 100,000 men/ year and 3.11 (CI 95%: 3.04- 3.18) hospitalizations per 100,000 men/ year, respectively during the study period.

 

The hospitalization rate increased significantly during the study period in all locations. It also increased significantly with age for all locations. Hospitalization and mortality rates in men were 50% higher than in women

A total of 530 deaths related to penis malignant neoplasm and 738 deaths related to anus malignant neoplasm in men and 488 in women were reported during the 12-y study period.

Although a decrease in smoking prevalence has led to a decrease in the incidence of cancers in the last decade, the hospitalizations due to anal and penile malign neoplasm have not declined in our study. This might be attributed to a high prevalence of HPV infection in these particular genital malign neoplasms.

Immunogenicity of a multi-epitope DNA vaccine against hantavirus

Chen Zhao, Ying Sun, Yujie Zhao, Si Wang, Tongtong Yu, Feng Du, X. Frank Yang and Enjie Luo
Pages 208 - 215
http://dx.doi.org/10.4161/hv.18389
Abstract | Full Text | PDF

Hemorrhagic fever with renal syndrome (HFRS) is a severe epidemic disease caused by hantaviruses including Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus. Three of the four HFRS hantaviruses, HTNV, SEOV, and PUUV are found in China. Currently, there is no effective strategy available to reduce infection risk. In this study, we constructed a multi-epitope chimeric DNA vaccine that encodes expressing 25 glycoprotein epitopes from SEOV, HTNV and PUUV (designated as SHP chimeric gene). Vaccination of BALb/c mice with SHP multi-epitope chimeric DNA vaccine led to a dramatic augmentation of humoral and cellular responses. The SHP vaccine DNA was detected in many organs but not for more than 60 d. There was no risk of mutation due to integration. Thus, the SHP multi-epitope chimeric DNA vaccine is a potential effective and safe DNA vaccine against infection by SEOV, HTNV, and PUUV.

Superior immunogenicity of seasonal influenza vaccines containing full dose of MF59^® adjuvant: Results from a dose-finding clinical trial in older adults

Giovanni Della Cioppa, Uwe Nicolay, Kelly Lindert, Geert Leroux-Roels, Frederic Clement, Flora Castellino, Grazia Galli, Nicola Groth and Giuseppe Del Giudice
Pages 216 - 227
http://dx.doi.org/10.4161/hv.18445
Abstract | Full Text | PDF

Background: MF59-adjuvanted influenza vaccines have superior immunogenicity in older adults compared with non-adjuvanted vaccines. We assessed whether changing formulation (i.e., increasing H3N2 antigen or decreasing the quantity of adjuvant) of the licensed, MF59-adjuvanted trivalent influenza subunit vaccine Fluad^® (Novartis Vaccines and Diagnostics) improves the risk-benefit profile in vaccinees aged ≥65 years.

 

Results: A significant dose-response relationship was observed between antibody levels and MF59 dose; full dose formulations elicited the strongest immune responses, meeting immunogenicity licensure criteria by Day 8. Doubling H3N2 antigen content did not increase the response to this antigen. Increased frequency of circulating CD4+ T-cells specific for vaccine antigens were detected by Day 8; magnitude and functional profile of the CD4+ T-cell response was comparable across the different vaccination groups. Mild to moderate solicited local reactions were more common with vaccines formulated with higher doses of MF59^®, but there were no MF59- or antigen dose-related increase in the frequency of solicited systemic reactions or unsolicited adverse events and serious adverse events.

Methods: We report on 357 subjects who received one of eight intramuscular vaccine formulations. Hemagglutination-inhibiting antibodies were assayed on Days 1, 8 and 22; magnitude and functional profile of CD4+ T-cell responses to vaccine antigens were assessed in subsets. Solicited adverse reactions were reported via diary cards for seven days after vaccination and spontaneous adverse events were monitored throughout the study.

Conclusion: This study confirms that the current formulation is the optimal one for MF59-adjuvanted influenza vaccine for use in older adults.

Are age-based strategies effective in increasing influenza vaccination coverage?: The Spanish experience

Rodrigo Jimenez-Garcia, Valentín Herńndez-Barrera, Cristina Rodríguez-Rieiro, Ana López de Andrés, Javier de Miguel-Diez, Isabel Jimenez Trujillo and Pilar Carrasco-Garrido
Pages 228 - 233
http://dx.doi.org/10.4161/hv.18433
Abstract | PDF

We investigated the effectiveness of applying age-based strategies to improve influenza vaccination coverage in Spain. We described and compared influenza vaccination coverage from 2003 to 2010 between those Spanish autonomous regions (AR) that lowered the age limit to 60 y and those regions that maintained the limit at 65 y.

 

We used data collected from two surveys covering a representative sample of the Spanish population aged ≥16 y [Spanish National Health Survey (SNHS) 2003/2004 and the European Health Survey for Spain (EHSS) 2009/2010].

The study population (persons aged ≥60 y) comprised 7,496 persons in the SNHS and 7,686 in the EHSS. In 2010, those AR which had reduced the age limit had higher coverage for all age groups analyzed—regardless of the presence of associated chronic conditions—than AR which continued vaccination for those ≥65 y. The greatest differences appeared in individuals aged 60 to 64 y (36.9% vs. 24.4% for individuals without chronic conditions, 59.1% vs. 52.9% for those with chronic conditions, and 43.3% vs. 32.3% for the entire age group).

Multivariate analysis showed that those AR which lowered the age limit increased total coverage for all age groups, specifically among individuals with chronic conditions aged 60 to 64 y (IRR 1.18; 95% CI, 1.01–1.54) and ≥65 y (IRR 1.07; 95% CI, 1.00–1.14). No significant changes were observed over time for the AR that continued vaccinating people aged ≥65 y. Our results suggest that age-based strategies are effective for improving influenza vaccination coverage in Spain.

National patterns in human papillomavirus vaccination: An analysis of the National Survey of Family Growth

Gelareh Sadigh, Amanda F. Dempsey, Mack Ruffin, Ken Resnicow and Ruth C. Carlos
Pages 234 - 242
http://dx.doi.org/10.4161/hv.18456
Abstract | PDF

Human papillomavirus (HPV) vaccine has shown effectiveness for girls and young women. Despite this, there are population disparities in vaccine utilization rates. The purpose of this study was to evaluate maternal correlates of HPV vaccination among their adolescent daughters using a nationally-representative population-based sample, emphasizing race/ethnicity-specific disparities and barriers. Mothers of 9–18 y-old girls having heard of HPV vaccine and completing the HPV vaccine survey module from the 2006–2008 National Survey of Family Growth (NSFG) (n = 444) were analyzed for maternally-reported adolescent HPV vaccination and maternal intent to vaccinate her adolescent daughter if no dose had been received. Correlates of uptake and intent were examined using multivariate logistic regression. 27% of mothers (n = 98) reported that their daughters were vaccinated against HPV. Independent correlates of vaccination included African-American race (adjusted odds ratio (AOR),0.29; 95% confidence interval (CI),0.11–0.77), and living below the poverty level (AOR,4.43; 95%CI, 1.53–12.82). 46% (n = 152) of mothers of non-vaccinated daughters intended to vaccinate them. Correlates of maternal intention included maternal pelvic exam history (AOR,0.06; 95%CI, 0.007–0.51), multiple male lifetime sexual partners (AOR,3.22 ; 95% CI, 1.34–7.76), religiosity (AOR,0.37; 95% CI,0.16–0.87) and acceptability of premarital sex among 18 y-olds (AOR,2.45; 95% CI, 1.16–5.20). In conclusion, HPV vaccination initiation among adolescent daughters of mothers participating in the NSFG continues to lag among African-American participants. However, no racial/ethnic differences in maternal intent-to-vaccinate her daughter were detected. Future interventions need to address specific maternal barriers to vaccine uptake and how these may differ from vaccine intention.

The cost efficiency of HPV vaccines is significantly underestimated due to omission of conisation-associated prematurity with neonatal mortality and morbidity

Philipp Soergel, Lars Makowski, Cordula Schippert, Ismini Staboulidou, Ursula Hille and Peter Hillemanns
Pages 243 - 251
http://dx.doi.org/10.4161/hv.18519
Abstract | PDF

Introduction: Cervical intraepithelial neoplasia (CIN) represents the precursor of invasive cervical cancer and is associated with human papillomavirus infection (HPV) against which two vaccines have been approved in the last years. Standard treatments of high-grade CIN are conisation procedures, which are associated with an increased risk of subsequent pregnancy complications like premature delivery and possible subsequent life-long disability. HPV vaccination has therefore the potential to decrease neonatal morbidity and mortality. This has not been taken into account in published cost-effectiveness models.

Material and Methods: We calculated the possible reduction rate of conisations for different vaccination strategies for Germany. Using this rate, we computed the reduction of conisation-associated preterm deliveries, life-long disability and neonatal death due to prematurity. The number of life-years saved (LYS) and gain in quality-adjusted life-years (QALYs) was estimated. The incremental costs per LYS / additional QALY were calculated.

Results: The reduction of conisation procedures was highest in scenario I (vaccination coverage 90% prior to HPV exposition) with about 50%. The costs per LYS or additional QALY were lowest in scenario I, II and III with 45,101 € or 43,505–47,855 € and rose up to 60,544 € or 58,401–64,240 € in scenario V (50% vaccinated prior to sexual activity + additional 20% catch-up at a mean age of 20 y).

Conclusion: Regarding the HPV 16 / 18 vaccines as “vaccines against conisation-related neonatal morbidity and mortality” alone, they already have the potential to be cost-effective. This effect adds up to reduction of cervical cancer cases and decreased costs of screening for CIN. Further studies on cost-effectiveness of HPV vaccination should take the significant amount of neonatal morbidity and mortality into account.

Improvement of influenza vaccine strain A/Vietnam/1194/2004 (H5N1) growth with the neuraminidase packaging sequence from A/Puerto Rico/8/34

Weiqi Pan, Zhenyuan Dong, Weixu Meng, Wei Zhang, Ting Li, Chufang Li, Beiwu Zhang and Ling Chen
Pages 252 - 259
http://dx.doi.org/10.4161/hv.18468
Abstract | Full Text | PDF

H5N1 influenza candidate vaccine viruses were developed using the “6+2” approach. The hemagglutinin (HA) and neuraminidase (NA) genes were derived from the popular H5N1 virus and the remaining six internal segments were derived from the A/Puerto Rico/8/34 strain (H1N1, PR8). However, some of these candidate strains have been reported to produce relatively low yields in vaccine manufacture. In this study, we found that the NA vRNA of the A/Vietnam/1194/2004 strain (H5N1, VN1194) was poorly packaged into recombinant viruses with a backbone of PR8 genes, which resulted in the formation of defective virions that did not include the NA vRNA in the genome. Using recombinant DNA techniques, we constructed a chimeric NA gene with the coding region of VN1194 NA flanked by the packaging signal sequence of the PR8 NA gene (41 bp form the 3′ end of the vRNA and 67 bp from the 5′ end). The packaging of the NA vRNA was restored to normal levels in the recombinant viruses containing the chimeric NA gene. Recombinant viruses containing the chimeric NA replicated much better in chicken embryonated eggs than viruses with the wild-type NA from VN1194. These findings suggest a novel strategy to improve in ovo growth of vaccine strains and to increase the number of vaccine doses available to save people if a pandemic were to occur.

Open Access Article

Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults

Hideyuki Ikematsu, Hideaki Nagai, Masahiro Kawashima, Yasunobu Kawakami, Kazuyoshi Tenjinbaru, Ping Li, Karl Walravens, Paul Gillard and François Roman
Pages 260 - 266
http://dx.doi.org/10.4161/hv.18469
Abstract | PDF

Background

Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612].

Methods

One-hundred healthy subjects aged 20−64 y (stratified [1:1] into two age strata 20−40 y and 41−64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75µg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here.

Results

Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile.

Conclusion

Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.




COMMENTARIES

Current cell-based influenza vaccine production technology as pandemic contingency

Say Kong Ng
Pages 267 - 271
http://dx.doi.org/10.4161/hv.18336
Abstract | PDF

Production technologies culminating in cell-based Influenza vaccines have been in development since the 1930s. It became a relevant technology for pandemic contingency after human infections by the highly pathogenic H5N1 avian Influenza viruses from 1997. Ten years from the first regulatory approvals in 2001, pandemic vaccines have been manufactured using this technology. However, the production capacity for cell-based Influenza vaccines is still inadequate to cater for a possible Influenza pandemic. One challenge for the expansion of cell-based Influenza vaccine production capacity is the uncertainty in the relevance of current cell-based Influenza vaccine production technology, because egg-based H5N1 vaccines are developed, and new Influenza vaccine technologies are in the pipeline. Nonetheless, cell-based Influenza vaccines are still relevant for the rapid production of new Influenza virus strains that can be challenging for egg-based production, and new vaccines based on current cell-based production technology will keep these relevant in the future. Another major challenge to expanding cell-based Influenza vaccine production capacity is the substantial investment required, coupled with possibly small returns because seasonal Influenza vaccines can be adequately supplied by existing egg-based facilities. This dilemma can be solved by motivating manufacturers of other cell-based therapeutics to set up on-demand production capabilities for cell-based pandemic Influenza vaccines in their existing facilities. This can reduce the investment and running costs, as well as decouple the production of pandemic vaccines from that of seasonal vaccines. With such approaches, current cell-based Influenza vaccine technologies can provide an economical solution to cater for the risk of an Influenza pandemic.

Rotavirus vaccine can save millions of children’s lives in developing countries

Ramesh Verma, Pardeep Khanna and Suraj Chawla
Pages 272 - 274
http://dx.doi.org/10.4161/hv.18390
Abstract | PDF

Rotavirus is a major cause of diarrhea-related morbidity and mortality in children worldwide. The virus is transmitted through feco-oral route. Its incubation period is about two days. Viral replication occurs in the villous epithelium of the small intestine. Immunodeficient children may have more severe or persistent disease and may have evidence of abnormalities in multiple organ systems, particularly the kidney and liver. Rotaviruses are also probably transmitted by other modes such as fomites, fecally contaminated food, water and respiratory droplets. Essentially every child in the world will have at least one rotavirus infection before age five. The diarrheal disease that caused by the rotavirus kills 500,000 children a year; >85 percent of those deaths are from developing countries. In India, 20% of all deaths in children < 5 y of age are due to diarrhea. It is further estimated that in India rotavirus causes around 100,000 deaths, and one out of 200 children under the age of 5 dies due to rotavirus annually. Improvements in sanitation and hygiene that stop many bacteria and parasites have not prevented the transmission of rotavirus. The vaccine has been launched in 62 countries and has been included the national immunization schedule in 11 countries. The Strategic Advisory Group of Experts (SAGE) recommends the inclusion of rotavirus vaccination of infants into all national immunization programs. The vaccine should be administered promptly after reconstitution as a 1ml oral dose. The vaccine should be given in two doses. The first dose should be administered at the age of 6 weeks and no later than at the age of 12 weeks. The interval between the 2 doses should be at least 4 weeks. Most of the high-disease-burden countries including India are eligible for Global Alliance for Vaccines and Immunization (GAVI) support to include such vaccines in national immunization program with nominal cost.

Perceptions of pandemic influenza vaccines

Cecile A. Marczinski
Pages 275 - 278
http://dx.doi.org/10.4161/hv.18457
Abstract | Full Text | PDF

Pandemic influenza A (H1N1) (pH1N1) was first identified in North America in early 2009. The pandemic flu outbreak during the 2009–2010 influenza season demonstrated how rapidly a new strain of flu can emerge and spread. Vaccination is the most effective method to prevent influenza, and vaccination during a pandemic is critical in limiting morbidity and mortality. Unfortunately, reports of vaccination rates for pH1N1 vaccines during the 2009–2010 influenza season indicated low rates for various demographic groups, including pregnant women, health care workers, child care workers, college students, and the general public. Furthermore, when asked about perceptions of pH1N1 vaccines, respondents in a variety of studies from the pH1N1 pandemic indicated common and universal misconceptions about influenza vaccines, especially in regard to perceptions of need, efficacy and safety. Therefore, if vaccination rates are to increase, an important outcome especially during pandemics, the psychological characteristics underpinning perceptions of influenza vaccines need to be understood better.




LETTERS

Open Access Article

Use of intranasal live attenuated influenza vaccine in individuals with asthma or a history of wheezing

Christopher S. Ambrose
Page 279
http://dx.doi.org/10.4161/hv.19585
Abstract | PDF




Open Access Article

Response to Christopher S. Ambrose: Use of live attenuated influenza vaccine in individuals with asthma or a history of wheezing

Susanna Esposito
Page 280
http://dx.doi.org/10.4161/hv.19661
PDF