[Show abstract][Hide abstract] ABSTRACT: Use of recently licensed vaccines against Neisseria meningitidis serogroup B (NmB) will depend partly on disease burden estimates. We systematically reviewed NmB incidence and mortality worldwide between January, 2000, and March, 2015, incorporating data from 37 articles and 12 websites. Most countries had a yearly invasive NmB incidence of less than 2 per 100 000 people. Within these relatively low incidence rates (compared with common causes of invasive bacterial diseases), substantial variation was detected between countries, with a notably higher incidence in Australia, Europe, North America, and South America. China and India had reports only of sporadic cases, and except for South Africa, sub-Saharan Africa showed a near absence of disease. In countries with consistently collected data, NmB incidence has tended to decrease, even as the proportion of invasive meningococcal disease cases caused by serogroup B has increased. With few exceptions, case-fatality ratios were fairly consistent, ranging between 3% and 10%. In high-income countries, incidence rates of NmB were relatively low compared with other vaccine-preventable diseases and might be decreasing. High case-fatality ratios, substantial disease-related morbidity, and the threat of outbreaks could nevertheless make NmB an attractive target for preventive and reactive immunisation programmes. The low availability of data from low-income and middle-income countries suggests the need for improved surveillance before vaccination strategies are designed.
[Show abstract][Hide abstract] ABSTRACT: Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization (WHO) regions were also reviewed. Findings are confounded by the lack of systematic and comparable observations in many areas of the world, but also by the cyclic nature of pertussis with peaks occurring every 3 to 5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country.
[Show abstract][Hide abstract] ABSTRACT: Cytomegalovirus vaccine development started in the 1970s with attenuated strains. In the 1980s, one of the strains was shown to be safe and effective in renal transplant patients. Then, attention switched to glycoprotein gB, which was shown to give moderate but transient protection against acquisition of the virus by women. The identification of the pp65 tegument protein as the principal target of cellular immune responses resulted in new approaches, particularly DNA, plasmids to protect hematogenous stem cell recipients. The subsequent discovery of the pentameric protein complex that generates most neutralizing antibodies led to efforts to incorporate that complex into vaccines. At this point, there are many candidate CMV vaccines, including live recombinants, replication-defective virus, DNA plasmids, soluble pentameric proteins, peptides, virus-like particles and vectored envelope proteins.
Medical Microbiology and Immunology 03/2015; 204(3). DOI:10.1007/s00430-015-0388-z · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
Proceedings of the National Academy of Sciences 08/2014; 111(34). DOI:10.1073/pnas.1400472111 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pertussis is resurgent in many countries, perhaps owing in part to waning immunity after acellular pertussis vaccination. We consider the options for improving current vaccines as well as other strategies to control pertussis.
[Show abstract][Hide abstract] ABSTRACT: Interview by Jenaid Rees (Commissioning Editor) Highly renowned in the vaccines world, Stanley A. Plotkin has worked at many leading institutions throughout his career, and is Emeritus Professor of the University of Pennsylvania and Adjunct Professor of the Johns Hopkins University. In 1991, Plotkin joined Sanofi Pasteur and worked there from 1991 to 1997, and now works as principal of Vaxconsult, LLC as a consultant to vaccine manufacturers, biotechnology companies and non-profit research organizations. Plotkin has served as chairman of the Infectious Diseases Committee and the AIDS Task Force of the American Academy of Pediatrics, liaison member of the Advisory Committee on Immunization Practices, and Chairman of the Microbiology and Infectious Diseases Research Committee of the National Institutes of Health. He has been a recipient of numerous prestigious medals and awards throughout his career, and his bibliography includes over 700 articles and several books, including the standard textbook on vaccines. He has worked extensively on the development and application of many vaccines including anthrax, oral polio, rabies, varicella and cytomegalovirus. He is also codeveloper of the newly licensed pentavalent rotavirus and is well-known for developing the rubella vaccine, now in standard use throughout the world.
[Show abstract][Hide abstract] ABSTRACT: Animal and human data from various viral infections and vaccine studies suggest that nonneutralizing antibodies (nNAb) without neutralizing activity in vitro may play an important in protection against viral infection in vivo. This was illustrated by the recent RV144 HIV vaccine efficacy trial, which demonstrated that binding HIV-specific IgG-mediated nNAb directed against the V2 loop of HIV-1 envelope (Env) were correlated inversely with risk for HIV acquisition while Env-specific plasma IgA-mediated antibodies were directly correlated with risk. However, Tier 1 NAb in the subset of responders with low plasma Env-specific IgA correlated with decreased risk. Non-human primate SIV and SHIV challenge studies suggest that Env-mediated antibodies are essential and sufficient for protection. A comparison of immune responses generated in human efficacy trials reveals subtle differences in the fine specificity of the antibody responses, in particular in HIV-specific IgG subclasses. The underlying mechanisms that may have contributed to protection against HIV acquisition in humans, although not fully understood, are possibly mediated by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or other non-neutralizing humoral effector functions such as antibody-mediated phagocytosis. The presence of such functional nNAb in mucosal tissues and cervico-vaginal and rectal secretions challenges the paradigm that NAb are the predominant immune response conferring protection, although this does not negate the desirability of evoking neutralizing antibodies through vaccination. Instead, NAb and nNAb should be looked as complementary or synergistic humoral effector functions. Several HIV vaccine clinical trials are on going to study these antibodies responses in various prime-boost modalities in the systemic and mucosal compartments. The induction of high frequency and titers of HIV-specific functional nNAb may represent an attractive hypothesis-testing strategy in future HIV vaccine efficacy trials.
[Show abstract][Hide abstract] ABSTRACT: Increasing evidence that the currently available acellular pertussis vaccines are not providing optimal control of pertussis in the United States and many other countries has stimulated interest in improvements of the current vaccines and in the development of new vaccines. A better understanding of the limitations of the current vaccines and the basis for the pertussis resurgence is needed to design improved vaccines. This article outlines several alternate approaches and summarizes the challenges related to the development of new or modified vaccines.
The Journal of Infectious Diseases 04/2014; 209 Suppl 1(suppl 1):S24-7. DOI:10.1093/infdis/jit531 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering pre-emptive antiviral therapy as an endpoint, because widespread use of pre-emptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccines, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection.
[Show abstract][Hide abstract] ABSTRACT: Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, tuberculosis, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances toward vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively generating vaccine-induced protective immune responses.
[Show abstract][Hide abstract] ABSTRACT: Publication of a report from the Institute of Medicine in 2000 showing that a vaccine against cytomegalovirus (CMV) would likely be cost saving was very influential and encouraged the clinical evaluation of candidate vaccines. The major objective of a CMV vaccination program would be to reduce disease caused by congenital CMV infection, which is the leading viral cause of sensorineural hearing loss and neurodevelopmental delay.CMV has challenges as a vaccine target because it is a herpesvirus, it persists lifelong despite host immunity, infected individuals can be reinfected with new strains, overt disease occurs in those with immature or impaired immune systems and persons with this infection do not usually report symptoms. Nevertheless, natural immunity against CMV provides some protection against infection and disease, natural history studies have defined the serological and molecular biological techniques needed for endpoints in future clinical trials of vaccines and CMV is not highly communicable, suggesting that it may not be necessary to achieve very high levels of population immunity through vaccination in order to affect transmission. Three phase 2 CMV vaccine studies have been completed in the last 3 years and all report encouraging outcomes.A key international meeting was organized by the Food and Drug Administration in January 2012 at which interested parties from regulatory bodies, industry and academia discussed and prioritised designs for phase 2 and phase 3 clinical trials. Vaccines able to prevent primary infection with CMV and to boost the immune response of those already infected are desirable. The major target populations for a CMV vaccine include women of childbearing age and adolescents. Toddlers represent another potential population, since an effect of vaccine in this age group could potentially decrease transmission to adults. In addition, prospective recipients of transplants and patients with AIDS would be expected to benefit.