Stanley A. Plotkin's research while affiliated with University of Pennsylvania and other places
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Publications (573)
Correlates of protection are key for vaccine development against any pathogen. In this paper we summarize recent information about correlates for vaccines against dengue, Ebola, influenza, pneumococcal, respiratory syncytial virus, rotavirus, shigella, tuberculosis and Zika virus.
Vaccine development has moved from an empirical origin to the use of antigenic characterization, structural biology, immune function definition, protein synthesis, and precise definition of immune correlates of protection in order to deal with more difficult biology of current targets.
Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS‐CoV‐2 coronavirus. Measurement of those antibodies by neutralization or binding assays both have predictive value, with binding antibody titers giving the highest statistical correlation. However, the protective functions of antibodies are multiple. Antibodie...
Some physicians and parents request to measure antimeasles serum IgG antibodies after measles-mumps-rubella (MMR) vaccination. Often, vaccine skeptical parents want to know if their child is "immune" after the first dose to avoid the second dose. In the usual healthy child, this should be discouraged for the following reasons. Commercially availabl...
Fake vaccines trafficking is a recent but growing phenomenon, which represents a severe threat to public health. During the Covid-19 pandemic, anti-Covid vaccines have been a prime target for traffickers, but all types of vaccines are falsified by profit-hungry criminals.
The consequences of falsification on global health are serious: decline in va...
Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with...
On 27 ̶ 29 July 2021, the National Institute of Allergy and Infectious Diseases (NIAID) hosted a virtual workshop on the topic of secondary vaccine effects to discuss existing evidence, potential immunological mechanisms and associated public health implications.
Rubella virus is the most teratogenic virus known to science and is capable of causing large epidemics. The RA 27/3 rubella vaccine, usually combined with measles vaccine, has eliminated rubella and congenital rubella syndrome from much of the world, notably from the Western Hemisphere. Except in immunosuppressed individuals, it is remarkably safe....
The COVID-19 pandemic has been devastating, but it enables us to learn from it and prepare for the next pandemic disease.
Correlates of protection for COVID-19 vaccines are urgently needed to license and deploy additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform calibrated to the international standard. IgG anti-Spike antibodies correlated significantly with efficacies for original virus an...
A correlate of protection (CoP) is urgently needed to expedite development of additional COVID-19 vaccines to meet unprecedented global demand. To assess whether antibody titers may reasonably predict efficacy and serve as the basis of a CoP, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccin...
Though eleven novel COVID-19 vaccines have demonstrated efficacy, additional affordable, scalable, and deliverable vaccines are needed to meet unprecedented global demand. With placebo-controlled efficacy trials becoming infeasible due to the roll out of licensed vaccines, a correlate of protection is urgently needed to provide a path for regulator...
WHO convened an Advisory Group (AG) to consider the feasibility, potential value and limitations of establishing a closely-monitored challenge model of experimental SARS-CoV-2 infection and COVID-19 in healthy adult volunteers. The AG included experts in design, establishment and performance of challenges. This report summarizes issues that render...
Over 100 attempts are being made to develop a vaccine for use in the epidemic of COVID-19. Many different technologies are being used in an effort to prevent the infection or at least the disease.
In the 20th century, the development, licensing and implementation of vaccines as part of large, systematic immunization programs started to address health inequities that existed globally. However, at the time of writing, access to vaccines that prevent life-threatening infectious diseases remains unequal to all infants, children and adults in the...
The Vaccine Compensation System evaluates true and false associations between vaccination and adverse events. The data from the system enable the calculation of the risk of serious adverse events per million doses given of each vaccine.
A licensed vaccine against dengue was shown to enhance disease under some circumstances, even though it protected most vaccinees. We discuss the implication of these results for the future of dengue vaccines.
The way to a successful vaccine against human cytomegalovirus is hampered by the peculiar biology of this infection. However, some candidate vaccines have been shown to protect seronegative women and transplant recipients, and we should know soon whether they can prevent congenital infection.
Numerous candidate vaccines against cytomegalovirus (CMV) infection and disease are in development. Whereas the previous article [1] provides background and opinions about the issues relating to vaccination, this article provides specifics about the vaccines in active development, as reported at a National Institutes of Health-sponsored meeting in...
Background:
Several cytomegalovirus (CMV) vaccine candidates are under development. To reduce the burden of congenital CMV infection, potential strategies under consideration include vaccination of adult women, adolescent girls, and/or young children (both sexes).
Methods:
We reviewed 5 studies that used infectious disease modeling to assess the...
Vaccines are everywhere hugely successful but are also under attack. The reason for the latter is the perception by some people that vaccines are unsafe. However that may be, vaccine safety, life any other scientific subject, must be constantly studied. It was from this point of view that a meeting was organized at the Wellcome Trust in London in M...
Substantial evidence has accumulated that "original antigenic sin" is a central factor shaping immune responses against influenza viruses. Here, we argue that this propensity of initial influenza virus exposure to establish a lifelong immunological imprint presents a remarkable opportunity: Immunization of infants prior to their initial, natural vi...
Correlates of protection (CoPs) are increasingly important in the development and licensure of vaccines. Although the study of CoPs was initially directed at identifying a single immune function that could explain vaccine efficacy, it has become increasingly clear that there are often multiple functions responsible for efficacy. This review is mean...
Mandatory immunization requirements protect both the individual and the community against the morbidity and mortality associated with vaccine-preventable illnesses. Despite the overwhelming evidence of safety and societal benefit, vaccines are associated with a small degree of risk to the individual of untoward reactions even when the vaccine is pr...
Pertussis is a vaccine-preventable disease that causes morbidity and mortality, particularly in infants and children <5 years of age. The Global Pertussis Initiative (GPI) recommendations represent a systematic evaluation and prioritization of strategies to prevent pertussis-related infant and child deaths, reduce global disease burden and prevent...
The introduction of a whole-cell vaccine against Bordetella pertussis, the causative agent of whooping cough, dramatically reduced disease incidence. Unfortunately, the whole-cell formulation also induces severe reactions in some infants. Because of this, acellular vaccines have been developed, but they are used exclusively in high-income countries...
Background and Objective
Pertussis remains among the leading vaccine-preventable diseases in many developed and developing countries, including those from the Americas region. The GPI is an expert scientific forum, which publishes consensus recommendations for pertussis monitoring, prevention, and treatment across many regions of the world. Here,...
The human cytomegalovirus (HCMV) is the most important infectious cause of congenital abnormalities and also of infectious complications of transplantation. The biology of the infection is complex and acquired immunity does not always prevent reinfection. Nevertheless, vaccine development is far advanced, with numerous candidate vaccines being test...
Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. Congenital HCMV (cCMV) infection is a major global contributor to long-term neurologic deficits, including deafness, microcephaly, neurodevelopmental delay, as well as fetal loss and occasional infant mort...
Vaccinations have had tremendous success in the 20th century. However, in the 21st century, we are facing complex immunological issues in relation to controlling underlying infectious diseases. Therefore, new technologies are needed to develop vaccines against infectious diseases like respiratory syncytial virus, human immunodeficiency virus, and c...
A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity in newborns, particularly sensorineural hearing loss (SNHL), and the public health impact of this infection on maternal and child health is under-recognized. Although progress toward development...
Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory resp...
Since the middle of the 20th century, vaccines have made a significant public health impact controlling infectious diseases globally. Although long-term protection has been achieved with some vaccines, immunity wanes over time with others, resulting in outbreaks or epidemics of infectious diseases. Long-term protection against infectious agents wit...
An immunological Correlate of Protection (CoP) is an immune response that is statistically interrelated with protection. Identification of CoPs for enteric vaccines would help design studies to improve vaccine performance of licensed vaccines in low income settings, and would facilitate the testing of future vaccines in development that might be mo...
The author reviews the foundation of the Coalition for Epidemic Preparedness and Innovations and the choices it has made for funding of vaccine development against epidemic diseases. He comments on those decisions as well as proposing how CEPI could remain relevant for the long term.
Pertussis is resurgent in some countries, particularly those in which children receive acellular pertussis (aP) vaccines in early infancy and boosters later in life. Immunologic studies show that, whereas whole-cell pertussis (wP) vaccines orient the immune system toward Th1/Th17 responses, acellular pertussis vaccines orient toward Th1/Th2 respons...
Despite the success of vaccines in reducing the morbidity and mortality associated with infectious diseases, many infectious diseases, both newly emerging and well known, lack vaccines. The global capability for beginning-to-end vaccine development has become limited, primarily owing to a scarcity of human capital necessary to guide the development...
Development of an efficacious HIV-1 vaccine is a major priority for improving human health worldwide. Vaccine-mediated protection against human pathogens can be achieved through elicitation of protective innate, humoral, and cellular responses. Identification of specific immune responses responsible for pathogen protection enables vaccine developme...
Background
Vaccination is a complex ecosystem with several components that interact with one another and with the environment. Today’s vaccine ecosystem is defined by the pursuit of polio eradication, the drive to get as many of the new vaccines to as many people as possible and the research and development against immunologically challenging disea...
The fourth roundtable meeting of the Global Influenza Initiative (GII) was held in Hong Kong, China, in July 2015. An objective of this meeting was to gain a broader understanding of the epidemiology, surveillance, vaccination policies and programs, and obstacles to vaccination of influenza in the Asia-Pacific region through presentations of data f...
Despite long-standing vaccination programs, substantial increases in reported cases of pertussis have been described in several countries during the last 5 years. Cases among very young infants who are at greatest risk of pertussis-related hospitalizations and mortality are the most alarming. Multiple hypotheses including but not limited to the ava...
Background
Cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.
Methods
The genomes of Towne and unattenuated Toledo strain were recombined yielding four Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received one subcutaneous dose at 10, 100,...
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 th...
Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000.
Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provid...
An international vaccine-development fund could provide the resources and momentum to carry vaccines from their conception to their development and licensure — thereby helping to avert a repetition of the Ebola crisis.
Vaccines already developed have been enormously successful. However, the development of future vaccines requires solution of a number of immunologic problems, including pathogen variability, short effector memory, evoking functional responses, and identification of antigens that generate protective responses. In addition, different populations may...
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 repor...
The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be...
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 th...
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.
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.
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...
Technological advances in antigen discovery, genomics and immunological monitoring offer tremendous potential for revolutionizing vaccine development. On 5-6 February 2014, 35 leading vaccine scientists met to consider how best to harness these advances and spur innovation.
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-media...
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 b...
Pertussis is resurgent, and many cases are occurring in vaccinated children and adolescents. In countries using acellular vaccines, waning immunity is at least part of the problem. This article discusses possible improvements in those vaccines. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society...
Citations
... This issue was also considered at the time of REMAP-CAP trial analyses when the emergence of Alpha variant became obvious [11] and which led to a substantial loss of efficacy of most available monoclonal antibody therapies [14]. We should also aim to determine the neutralising antibody threshold for effective CP treatment, similar to what has been previously determined for vaccine efficacy [15]. ...
... Driven by the utmost 65 importance of SARS-CoV-2, the characterization of infection 11 and vaccine immunity [12][13][14] recently attracted great interest. Animal models and correlative data suggest, that antibodies might protect from re-infection with the same virus variant whereas numbers and activity of CD8 + and CD4 + Tcells determine the severity of the disease 9,11,[15][16][17][18][19][20][21][22][23][24] . T-cell mediated protection is considered less susceptible to immune evasion caused by novel virus variants compared to protection by 70 neutralizing antibodies 9,16,19,[25][26][27] . ...
... Die Bestimmung von Antikörperkonzentrationen bzw. Titern nach Impfungen sollte regelhaft auf die von der STIKO definierten Situationen begrenzt und gut begründet sein [10]. ...
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... Public health programs, which could have effectively reduced the occurrence of vaccine preventable diseases, were affected and under public suspicion. Additionally hoax and rumors were circulating in the internet could have added to the vaccine hesitancy and possibly the rate of vaccine refusal as well as negative impression of the public health system and its programs [23,33,34]. ...
... The user was required to input the date of their second BNT162b2 vaccine dose, the date of their antibody titer measurement, the type of reagent used for the antibody titer measurement, and the antibody titer. Subsequently, the antibody dynamic was simulated by the model built into the application, and the estimated date on which the antibody titers would become lower than 154 BAU/mL, which was the protective antibody threshold proposed by Goldblatt et al. 13 , was displayed ( Fig. 4 and Supplementary video). The protective antibody threshold was still to be fixed; it could be variable based on the epidemic variants. ...
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... Furthermore, studies were not usually designed to specifically address the question of inter-dose interval. Rodrigues and Plotkin reviewed several trials of vaccination against human Papilloma virus, varicella-zoster virus, polio virus, and pneumococcus, and compared available data on antibody titres which were obtained using different inter-dose intervals [93]. The consensus emerging from this analysis was that a delayed prime/boost interval resulted in higher antibody titres, at least when a booster was administered within 6 months [93]. ...
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... syndrome (CRS) [2,3]. Rubella and CRS cases have declined in many countries owing to vaccination; however, they remain a concern, not only in Africa and Southeast Asia, where vaccination coverage is relatively low, but also in Japan, where large epidemics occurred in the last decade because of low vaccination coverage among certain populations [4][5][6]. Therefore, there is an ongoing effort to eliminate rubella globally [4]. ...
... However, individuals become less vigilant and choose not to comply with public measures if epidemic is not serious [37,38,39,40,41]. In other words, it is assumed that cooperators enhance the environment, replete environment breeds defection, then defectors destroy the environment and depleted environment is conductive to evolution of cooperators in evolutionary game with feedback mechanism [42,43,44,45]. ...
... Passive antibody transfer has proven protective in both non-human primate animal models and in the early treatment of some patients [13][14][15] . Correlates of protection have been proposed for both binding and neutralizing antibodies 8,16,17 . In parallel, a role for cell-mediated immunity which is intrinsically more crossprotective 18 , has been suggested for viral clearance and prevention of serious disease, as well as for long-term immunity 14,[19][20][21] . ...
... Studies of the relationship between neutralising antibodies and protection from symptomatic SARS-CoV-2 infection have shown that neutralising antibody titres are highly predictive of vaccine efficacy [4][5][6][7]14,15 and that a titre of~20% of the early convalescent level is associated with 50% protection from symptomatic infection 4 . This relationship predicted that a decline in neutralising antibody titres, either as a result of waning immunity or changes in SARS-CoV-2 viral variants, will lead to reduced vaccine protection against COVID-19 4 . ...
