Stanley A. Plotkin’s research while affiliated with University of Pennsylvania and other places

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Publications (606)


Inactivated Polio Vaccine Must Be an Essential Part of Polio Eradication
  • Article

May 2025

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1 Read

Clinical Infectious Diseases

Konstantin Chumakov

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Stanley A Plotkin



A vaccine against cytomegalovirus: how close are we?
  • Article
  • Full-text available

January 2025

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46 Reads

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3 Citations

The Journal of clinical investigation

The pursuit of a vaccine against the human cytomegalovirus (HCMV) has been ongoing for more than 50 years. HCMV is the leading infectious cause of birth defects, including damage to the brain, and is a common cause of complications in organ transplantation. The complex biology of HCMV has made vaccine development difficult, but a recent meeting sponsored by the National Institute of Allergy and Infectious Diseases in September of 2023 brought together experts from academia, industry, and federal agencies to discuss progress in the field. The meeting reviewed the status of candidate HCMV vaccines under study and the challenges in clinical trial design in demonstrating efficacy against congenital CMV infection or the reduction of HCMV disease following solid organ transplantation or hematopoietic stem cell transplantation. Discussion in the meeting revealed that, with the numerous candidate vaccines that are under study, it is clear that a safe and effective HCMV vaccine is within reach. Meeting attendees achieved a consensus opinion that even a partially effective vaccine would have a major effect on the global health consequences of HCMV infection.

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The Current and Future State of Vaccines for Lyme Disease

December 2024

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25 Reads

Clinical Infectious Diseases

Lyme disease is caused by Borrelia species that are transmitted by Ixodes ticks prevalent in parts of the United States and Europe. A Lyme vaccine containing the OspA antigens from the single Borrelia species most prevalent in the United States was marketed in the 1990s, but was withdrawn because of unproven concerns about safety, which led to insufficient sales. Since then, the incidence of Lyme disease has increased in the United States owing to the geographical spread of infected ticks. Lyme disease due to multiple different species of Borrelia also is widely prevalent in many European countries. New Lyme vaccines, using OspA antigens from multiple species of American and European Borrelia, are in advanced clinical development, and one such vaccine is in phase 3 trials. When licensed, new vaccines are likely to have an impact in preventing Lyme disease, although the need for periodic boosters remains to be defined.


Structure-based design of glycoprotein subunit vaccines for mumps

November 2024

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15 Reads

Proceedings of the National Academy of Sciences

Rebecca J. Loomis

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Sun B. Sowers

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[...]

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Guillaume B. E. Stewart-Jones

Mumps virus (MuV) is a highly contagious paramyxovirus that is endemic in most regions of the world and continues to cause outbreaks even in highly immunized populations. Outbreaks of mumps in countries with high measles, mumps, and rubella vaccination coverage have been attributed to waning immunity and antigenic differences between the Jeryl Lynn vaccine strain (genotype A) and circulating wild-type viruses. To obtain a subunit vaccine, we used structure-based design to engineer the mumps fusion (F) glycoprotein stabilized in its prefusion conformation (Pre-F) as well as a chimeric immunogen comprising Pre-F linked to mumps hemagglutinin neuraminidase (HN); in mice, both Pre-F antigen and the chimeric antigen elicited potent cross-reactive plaque reducing neutralizing titers to genotypes A, G, and H mumps. A crystal structure of mumps Pre-F at 2.16 Å resolution validated the stabilization strategy, while a post-fusion form of F was engineered as a comparator. Monoclonal antibodies to mumps Pre-F and HN were isolated from immunized mice; 7 of 14 Pre-F-specific antibodies and 9 of 15 HN-specific antibodies were capable of neutralizing genotype G MuV with a range of potencies. Additionally, 7 of 14 Pre-F-specific antibodies neutralized genotype A mumps. Structural and binding analyses of Pre-F-specific antibodies revealed binding to four discrete neutralizing antigenic sites and binding analyses of HN-specific antibodies revealed binding to five discrete neutralizing antigenic sites. Overall, the PreF and the chimeric Pre-F/HN immunogens are promising candidates to boost MMR-elicited immunity to mumps or as a next-generation vaccine.


Beyond Awareness: Hope for a CMV Vaccine! An Introduction to the Conference, “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

October 2024

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28 Reads

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children. The major theme of this National Institute of Allergy and Infectious Diseases (NIAID) workshop, “CMV Vaccine Development—How Close Are We?”, was to report progress on the development of a pre-conception vaccine that could confer protective immunity for women of child-bearing age. Such a vaccine could result in a reduced cCMV disease burden, although other populations, including solid organ transplant and hematopoietic stem cell transplant patients, could benefit as well. To frame the compelling need for a cCMV vaccine, a keynote lecture by Dr. Megan Pesch, immediate past-president of the National CMV Foundation and a leading cCMV researcher from the University of Michigan, was given. This manuscript provides a summary of Dr. Pesch’s presentation from this workshop, which was written as the introductory conference report for the meeting.


CMV vaccine candidates and key points.
Cont.
Proceedings of the Conference “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

October 2024

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36 Reads

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3 Citations

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children, including sensorineural hearing loss. There is interest in developing a pre-conception vaccine that could confer protective immunity on a woman of child-bearing age, hence resulting in a reduced cCMV disease burden. Other populations, including solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients, could also benefit from CMV vaccination. To review and discuss vaccines that are in clinical development, a workshop, sponsored by the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), was empaneled. At this workshop, correlates of protective immunity against CMV, epidemiologic features of CMV transmission, and vaccine platforms in development were reviewed. Representatives from academia, pharma, and the NIH engaged in discussion on the current state-of-the-art in CMV vaccinology. A summary of the presentations from this is provided in this report.



Citations (76)


... In this review, we do not intend to provide an exhaustive review of all HCMV vaccines, as this has been covered excellently by colleagues in the field-including a very interesting review of a recent NIH meeting involving key stakeholders in the HCMV vaccine field [27]. That said, we will highlight aspects of past and ongoing HCMV vaccination strategies and associated challenges, including a more detailed focus on recent advancements in the analyses of gB/MF59-the most successful vaccine candidate to date-and the implications for HCMV vaccination in general. ...

Reference:

Developing a Vaccine Against Human Cytomegalovirus: Identifying and Targeting HCMV’s Immunological Achilles’ Heel
A vaccine against cytomegalovirus: how close are we?

The Journal of clinical investigation

... Because HCMV is species-specific [4], animal models of infection by nonhuman CMVs such as murine CMV (MCMV) infection in mice have been used to provide insight into our understanding of HCMV infection in humans and to help develop vaccines against CMV infection [7,8]. A wide array of anti-CMV vaccines, such as virus-like particle (VLP) or subviral dense body vaccines, inactivated whole-viral-antigen vaccines, DNA vaccines, recombinant protein vaccines, and vaccines based on live attenuated virus vectors, have been tested in animals and humans [1,2,9]. In particular, some of these vaccines, when tested in mice challenged with MCMV, induced excellent immune responses and provide immune protection from MCMV challenge [10][11][12][13][14]. ...

Proceedings of the Conference “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

... Furthermore, integrating new vaccines into existing formulations, such as pentavalent or hexavalent vaccines, can reduce the frequency of injections, thereby enhancing caregiver compliance and health worker efficiency. This strategy aligns with global evidence advocating for reduced injection frequencies to optimize programmatic outcomes [20,25]. This study has several limitations that should be considered while interpreting the findings. ...

Why Combination Vaccines Are Necessary
  • Citing Article
  • September 2024

The Pediatric Infectious Disease Journal

... The effectiveness of V116 in this population will need confirmation through future real-world observational studies. In addition, post-marketing experience will be important to further characterize the safety and effectiveness of V116 in larger, more representative real-world populations than those available in clinical trials [75,76]. ...

Funding Postauthorization Vaccine-Safety Science
  • Citing Article
  • July 2024

The New-England Medical Review and Journal

... Immune CoPs can accelerate vaccine development by uncovering markers predictive of vaccine efficacy; such a tool can help identify promising early-stage candidates and facilitate evidence-based progression from late-stage trials to licensure (45). Defining CoPs for NV requires an understanding of mucosal immunity and its relationship to systemic immunity and vaccine effectiveness (45). ...

Realising the potential of correlates of protection for vaccine development, licensure and use: short summary

npj Vaccines

... Mumps vaccine policy of 2 doses with a booster at an older age would therefore help reduce the burden of disease in the community by reducing secondary attack rate as well as reducing the severe complications in adolescents. A novel and safe mumps vaccine with persistent attenuation and immunogenicity might be a potential solution to avoid a third dose in children [15]. ...

We Need a New Mumps Vaccine
  • Citing Article
  • February 2024

The Pediatric Infectious Disease Journal

... Intrauterine rubella infection during early pregnancy may cause a spectrum of congenital anomalies collectively termed Congenital Rubella Syndrome (CRS) [2]. CRS is an evitable yet critical condition linked with structural and functional irregularity like sensorineural deafness, cataracts, congenital heart disease, microcephaly, hepatosplenomegaly, and neurodevelopmental disabilities [3][4][5]. ...

The path to eradication of rubella
  • Citing Article
  • November 2023

Vaccine

... The clinical efficacy and effectiveness of vaccines are beyond question, with a wealth of scientific evidence demonstrating their ability to reduce disease incidence and prevalence, prevent severe health complications, and save lives. Concerning the clinical benefits of vaccination, vaccines are considered the health intervention with the greatest impact on reducing mortality and controlling population growth, second only to access to safe water [10][11][12][13][14][15][16][17][18]. ...

A Short History of Vaccination
  • Citing Chapter
  • January 2023

... various cell types-dendritic cells, T cells, B cells-and the molecular signals they exchange, such as cytokines and chemokines (67). Determining correlates of protection therefore presents a significant challenge in the field of vaccine development (68)(69)(70)(71) and requires principled statistical analysis based on an understanding of the underlying immunological mechanisms. The heterogeneity of data sources and the nuances of individual immune responses pose obstacles to the reliable evaluation of CoPs, making it a specialized and challenging aspect of vaccine research. ...

Correlates of Protection
  • Citing Chapter
  • January 2023

... Subunit or mRNA vaccines offer the potential to circumvent these two limitations to wide implementation. Firstly, shingles, HPV and SARS-CoV-2 vaccines are immunogenic in aged populations, in immunocompromised patients and in patients with cancer 12,30,35 . This implies that existing commercial vaccines could be effectively used in a priming phase prior to IT injection to boost and normalize the level of preexisting T cell responses. ...

State-of-the-Science of Human Papillomavirus Vaccination in Women with Human Immunodeficiency Virus: Summary of a Scientific Workshop
  • Citing Article
  • July 2023

Preventive Medicine Reports