Publications by authors named "Jose Esparza"

47 Publications

Re-assembly of nineteenth-century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the USA.

Genome Biol 2020 Dec 4;21(1):286. Epub 2020 Dec 4.

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373 - CCS, Ilha do Fundão, Rio de Janeiro, RJ, 21941-590, Brazil.

According to a recent article published in Genome Biology, Duggan and coworkers sequenced and partially assembled five genomes of smallpox vaccines from the nineteenth century. No information regarding the ends of genomes was presented, and they are important to understand the evolutionary relationship of the different smallpox vaccine genomes during the centuries. We re-assembled the genomes, which include the largest genomes in the vaccinia lineage and one true horsepox strain. Moreover, the assemblies reveal a diverse genetic structure in the genome ends. Our data emphasize the concurrent use of horsepox and horsepox-related viruses as the smallpox vaccine in the nineteenth century.
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http://dx.doi.org/10.1186/s13059-020-02202-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716468PMC
December 2020

Ethical conflicts in COVID-19 times.

J Infect Dev Ctries 2020 09 30;14(9):968-970. Epub 2020 Sep 30.

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States.

The COVID-19 pandemic has created new challenges on multiple fronts including a few ethical concerns. Timely and appropriate access to health services and the need to protect vulnerable people are some of them. An important aspect to consider, at the global level, is the frailty of health systems in many developing countries and the constant threat of these collapsing due to shortage of resources and medical supply. Special attention should be placed towards protecting the health of care workers who are highly exposed to SARS-CoV-2 infection. Research and clinical trials involving COVID-19 patients and healthy human volunteers must be done in strict adherence to the fundamental principles of bioethics, even if finding a solution is an urgent need. Shared responsibility must be assumed as we collectively face a common problem and ethical conflicts must be resolved using, as reference, the guidelines developed by the World Health Organization and other relevant international and national organizations. This would allow responsible action in the face of the pandemic without harming human rights, the individual and collective well-being.
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http://dx.doi.org/10.3855/jidc.13137DOI Listing
September 2020

Lessons From History: What Can We Learn From 300 Years of Pandemic Flu That Could Inform the Response to COVID-19?

Authors:
José Esparza

Am J Public Health 2020 08;110(8):1160-1161

José Esparza is with the Institute of Human Virology, University of Maryland School of Medicine, Baltimore, and the Robert Koch Institute, Berlin, Germany.

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http://dx.doi.org/10.2105/AJPH.2020.305761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349423PMC
August 2020

Early smallpox vaccine manufacturing in the United States: Introduction of the "animal vaccine" in 1870, establishment of "vaccine farms", and the beginnings of the vaccine industry.

Vaccine 2020 06 27;38(30):4773-4779. Epub 2020 May 27.

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

For the first 80-90 years after Jenner's discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as "animal vaccine", which referred to growing vaccine material from serial propagation in calves before use in humans. The use of "animal vaccine" had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The "animal vaccine" concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of "vaccine farms" were established in the U.S. and produced large quantities of "animal vaccine". These "vaccine farms" were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The "vaccine farms" evolved from producing only smallpox "animal vaccine" to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox "animal vaccines". Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as "variants" more appropriately than "strains". Further, clonal analysis of modern "animal vaccines" indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox.
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http://dx.doi.org/10.1016/j.vaccine.2020.05.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294234PMC
June 2020

Three different paths to introduce the smallpox vaccine in early 19th century United States.

Authors:
José Esparza

Vaccine 2020 03 11;38(12):2741-2745. Epub 2020 Feb 11.

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:

The ancient technique of variolation (inoculation of the smallpox) which was introduced in the United States in 1721 was replaced by vaccination (inoculation of the cowpox) soon after the procedure was published by Edward Jenner in 1798. Benjamin Waterhouse is recognized as the introducer of smallpox vaccination in the United States having conducted the first vaccination in Boston on 8 July 1800, although other American physicians also played an important role in extending vaccination in the East Coast of the United States. A different route of introduction brought the smallpox vaccine from Mexico to New Mexico (March 1805) and Texas (April 1806) which at that time where part of the Viceroyalty of New Spain. The vaccine was brought to California in 1817 by Russian merchants who obtained it in Peru, where the vaccine had arrived in 1806 with the Spanish Philanthropic Expedition of the Vaccine. It took almost 150 years of vaccination efforts before the last natural outbreak of smallpox occurred in the United States in 1949.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.077DOI Listing
March 2020

Early vaccine advocacy: Medals honoring Edward Jenner issued during the 19th century.

Authors:
José Esparza

Vaccine 2020 02 12;38(6):1450-1456. Epub 2019 Dec 12.

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:

The results from the first vaccination experiments published by Edward Jenner in 1798 were widely disseminated and consequently Jennerian vaccination was rapidly introduced in Europe and elsewhere. One of the reasons for the rapid spread of vaccination was that Jenner championed the procedure as a public health tool and not just as a mean to achieve individual protection. Vaccination was promoted by the highest levels of government in Germany where the vaccine was introduced in 1799 and also in France, where the vaccine arrived in 1800. Medals were used to promote vaccination both rewarding parents of vaccinated children as well as meritorious vaccinators. The first medal mentioning the name of Jenner was minted in Germany in 1803 followed by others, minted in Germany, Italy, France and England. Numerous other vaccine medals were made during the 19th century as an early and little known approach to advocating for vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2019.11.077DOI Listing
February 2020

Beyond the myths: Novel findings for old paradigms in the history of the smallpox vaccine.

PLoS Pathog 2018 07 26;14(7):e1007082. Epub 2018 Jul 26.

Laboratório de Biologia Molecular de Virus, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

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http://dx.doi.org/10.1371/journal.ppat.1007082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062137PMC
July 2018

Role of Melatonin in Aluminum-Related Neurodegenerative Disorders: a Review.

Biol Trace Elem Res 2019 Mar 7;188(1):60-67. Epub 2018 May 7.

Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Catalonia, Spain.

Aluminum (Al), a potentially neurotoxic element, provokes various adverse effects on human health such as dialysis dementia, osteomalacia, and microcytic anemia. It has been also associated with serious neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and Parkinsonism dementia of Guam. The "aluminum hypothesis" of AD assumes that the metal complexes can potentiate the rate of aggregation of amyloid-β (Aβ), enhancing the toxicity of this peptide, and being able of contributing to the pathogenesis of AD. It has been supported by a number of analytical, epidemiological, and neurotoxicological studies. On the other hand, melatonin (Mel) is a potent direct free radical scavenger and indirect antioxidant, which acts increasing the activity of important related antioxidant enzymes, and preventing oxidative stress and cell death of neurons exposed to Aβ-induced neurotoxicity. Therefore, Mel might be useful in the treatment of AD by reducing the Aβ generation and by inhibiting mitochondrial cell death pathways. The present review on the role of Mel in Al-related neurodegenerative disorders concludes that the protective effects of this hormone, together with its low toxicity, support the administration of Mel as a potential supplement in the treatment of neurological disorders, in which oxidative stress is involved.
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http://dx.doi.org/10.1007/s12011-018-1372-4DOI Listing
March 2019

Intragastric Administration of Lactobacillus plantarum and 2,2'-Dithiodipyridine-Inactivated Simian Immunodeficiency Virus (SIV) Does Not Protect Indian Rhesus Macaques from Intrarectal SIV Challenge or Reduce Virus Replication after Transmission.

J Virol 2018 05 27;92(10). Epub 2018 Apr 27.

Emory Vaccine Center, Emory University, Atlanta, Georgia, USA

A major obstacle to development of an effective AIDS vaccine is that along with the intended beneficial responses, the immunization regimen may activate CD4 T cells that can facilitate acquisition of human immunodeficiency virus (HIV) by serving as target cells for the virus. Lu et al. (W. Lu et al., Cell Rep 1736-1746, 2012, https://doi.org/10.1016/j.celrep.2012.11.016) reported that intragastric administration of chemically inactivated simian immunodeficiency virus SIV and (iSIV-) protected 15/16 Chinese-origin rhesus macaques (RMs) from high-dose intrarectal SIV challenge at 3 months postimmunization. They attributed the observed protection to induction of immune tolerance, mediated by "MHC-Ib/E-restricted CD8 regulatory T cells that suppressed SIV-harboring CD4 T cell activation and SIV replication in 15/16 animals without inducing SIV-specific antibodies or cytotoxic T." J.-M. Andrieu et al. (Front Immunol 5:297, 2014, https://doi.org/10.3389/fimmu.2014.00297) subsequently reported protection from infection in 23/24 RMs immunized intragastrically or intravaginally with iSIV and BCG, , or , which they ascribed to the same tolerogenic mechanism. Using vaccine materials obtained from our coauthors, we conducted an immunization and challenge experiment with 54 Indian RMs and included control groups receiving iSIV only or only as well as unvaccinated animals. Intrarectal challenge with SIV resulted in rapid infection in all groups of vaccinated RMs as well as unvaccinated controls. iSIV-vaccinated animals that became SIV infected showed viral loads similar to those observed in animals receiving iSIV only or only or in unvaccinated controls. The protection from SIV transmission conferred by intragastric iSIV- administration reported previously for Chinese-origin RMs was not observed when the same experiment was conducted in a larger cohort of Indian-origin animals. Despite an increased understanding of immune responses against HIV, a safe and effective AIDS vaccine is not yet available. One obstacle is that immunization may activate CD4 T cells that may act as target cells for acquisition of HIV. An alternative strategy may involve induction of a tolerance-inducing response that limits the availability of activated CD4 T cells, thus limiting the ability of virus to establish infection. In this regard, exciting results were obtained for Chinese-origin rhesus macaques by using a "tolerogenic" vaccine, consisting of intragastric administration of and 2,2'-dithiodipyridine-inactivated SIV, which showed highly significant protection from virus transmission. In the present study, we administered iSIV- to Indian-origin rhesus macaques and failed to observe any protective effect on virus acquisition in this experimental setting. This work is important because it contributes to the overall assessment of the clinical potential of a new candidate AIDS vaccine platform based on iSIV-.
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http://dx.doi.org/10.1128/JVI.02030-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923080PMC
May 2018

Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine.

Vaccine 2017 12 11;35(52):7222-7230. Epub 2017 Nov 11.

Centre for Biological Threats and Special Pathogens 1 - Highly Pathogenic Viruses & German Consultant Laboratory for Poxviruses & WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany.

For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that "matter" obtained from either disease could be used as preventative of smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced smallpox vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.
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http://dx.doi.org/10.1016/j.vaccine.2017.11.003DOI Listing
December 2017

An Early American Smallpox Vaccine Based on Horsepox.

N Engl J Med 2017 10;377(15):1491-1492

Robert Koch Institute, Berlin, Germany

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http://dx.doi.org/10.1056/NEJMc1707600DOI Listing
October 2017

Reducing the global burden of HTLV-1 infection: An agenda for research and action.

Antiviral Res 2017 01 11;137:41-48. Epub 2016 Nov 11.

St. Marianna University School of Medicine, Kanagawa, Japan.

Even though an estimated 10-20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines.
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http://dx.doi.org/10.1016/j.antiviral.2016.10.015DOI Listing
January 2017

Emerging viral epidemics and pandemics: What will be the next?

Authors:
José Esparza

Invest Clin 2016 Sep;57(3):231-5

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September 2016

Evaluating the value proposition for improving vaccine thermostability to increase vaccine impact in low and middle-income countries.

Vaccine 2015 Jul 6;33(30):3471-9. Epub 2015 Jun 6.

Vaccine Delivery, Global Health, The Bill & Melinda Gates Foundation, Seattle, WA, USA.

The need to keep vaccines cold in the face of high ambient temperatures and unreliable access to electricity is a challenge that limits vaccine coverage in low and middle-income countries (LMICs). Greater vaccine thermostability is generally touted as the obvious solution. Despite conventional wisdom, comprehensive analysis of the value proposition for increasing vaccine thermostability has been lacking. Further, while significant investments have been made in increasing vaccine thermostability in recent years, no vaccine products have been commercialized as a result. We analyzed the value proposition for increasing vaccine thermostability, grounding the analysis in specific vaccine use cases (e.g., use in routine immunization [RI] programs, or in campaigns) and in the broader context of cold chain technology and country level supply chain system design. The results were often surprising. For example, cold chain costs actually represent a relatively small fraction of total vaccine delivery system costs. Further, there are critical, vaccine use case-specific temporal thresholds that need to be overcome for significant benefits to be reaped from increasing vaccine thermostability. We present a number of recommendations deriving from this analysis that suggest a rational path toward unlocking the value (maximizing coverage, minimizing total system costs) of increased vaccine thermostability, including: (1) the full range of thermostability of existing vaccines should be defined and included in their labels; (2) for new vaccines, thermostability goals should be addressed up-front at the level of the target product profile; (3) improving cold chain infrastructure and supply chain system design is likely to have the largest impact on total system costs and coverage in the short term-and will influence the degree of thermostability required in the future; (4) in the long term, there remains value in monitoring the emergence of disruptive technologies that could remove the entire RI portfolio out of the cold chain.
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http://dx.doi.org/10.1016/j.vaccine.2015.05.071DOI Listing
July 2015

A New Scientific Paradigm may be Needed to Finally Develop an HIV Vaccine.

Authors:
José Esparza

Front Immunol 2015 18;6:124. Epub 2015 Mar 18.

Institute of Human Virology, University of Maryland School of Medicine , Baltimore, MD , USA.

The bulk of current HIV vaccine research is conducted within the infectious disease paradigm that has been very successful in developing vaccines against many other viral diseases. Different HIV vaccine concepts, based on the induction of neutralizing antibodies and/or cell mediated immunity, have been developed and clinically tested over the last 30 years, resulting in a few small successes and many disappointments. As new scientific knowledge is obtained, HIV vaccine concepts are constantly modified with the hope that the newly introduced tweaks (or paradigm drifts) will provide the solution to one of the most difficult challenges that modern biomedical research is confronting. Efficacy trials have been critical in guiding HIV vaccine development. However, from the five phase III efficacy trials conducted to date, only one (RV144) resulted in modest efficacy. The results from RV144 were surprising in many ways, including the identified putative correlates of protection (or risk), which did not include neutralizing antibodies or cytotoxic T-cells. The solution to the HIV vaccine challenge may very well come from approaches based on the current paradigm. However, at the same time, out-of-the-paradigm ideas should be systematically explored to complement the current efforts. New mechanisms are needed to identify and support the innovative research that will hopefully accelerate the development of an urgently needed HIV vaccine.
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http://dx.doi.org/10.3389/fimmu.2015.00124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364287PMC
April 2015

The prevention and eradication of smallpox: a commentary on Sloane (1755) 'An account of inoculation'.

Philos Trans R Soc Lond B Biol Sci 2015 Apr;370(1666)

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called 'variolation') involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox ('vaccination') followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these 'weapons of mass protection'. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.
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http://dx.doi.org/10.1098/rstb.2014.0378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360126PMC
April 2015

More Surprises in the Development of an HIV Vaccine.

Front Immunol 2014 14;5:329. Epub 2014 Jul 14.

CNRS, UMR7242-Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg (IREBS), Université de Strasbourg , Illkirch-Graffenstaden , France.

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http://dx.doi.org/10.3389/fimmu.2014.00329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095567PMC
July 2014

Has horsepox become extinct?

Authors:
José Esparza

Vet Rec 2013 Sep;173(11):272-3

Senior Advisor, Global Health (Vaccines), Bill & Melinda Gates Foundation, Seattle, Washington, USA.

Mystery surrounds the extent to which horsepox virus may have contributed to the vaccinia virus used to eradicate smallpox. With few documented cases of horsepox in recent years it may never be solved, says José Esparza, who seeks to raise awareness of the potential historical and  scientific importance of identifying new cases.
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http://dx.doi.org/10.1136/vr.f5587DOI Listing
September 2013

A brief history of the global effort to develop a preventive HIV vaccine.

Authors:
José Esparza

Vaccine 2013 Aug 21;31(35):3502-18. Epub 2013 May 21.

Bill & Melinda Gates Foundation, PO Box 23350, Seattle, WA 98102, USA.

Soon after HIV was discovered as the cause of AIDS in 1983-1984, there was an expectation that a preventive vaccine would be rapidly developed. In trying to achieve that goal, three successive scientific paradigms have been explored: induction of neutralizing antibodies, induction of cell mediated immunity, and exploration of combination approaches and novel concepts. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. In 2009, the field was reinvigorated with the modest results obtained from the RV144 trial conducted in Thailand. Here, we review those vaccine development efforts, with an emphasis on events that occurred during the earlier years. The goal is to provide younger generations of scientists with information and inspiration to continue the search for an HIV vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2013.05.018DOI Listing
August 2013

Progress in the development of an adenovirus 26 vector platform for HIV vaccines.

Authors:
José Esparza

Expert Rev Vaccines 2013 May;12(5):477-80

Bill & Melinda Gates Foundation, PO Box 23350, Seattle, WA 98102, USA.

Evaluation of: Baden LR, Walsh SR, Seaman MS et al. First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env Vaccine (IPCAVD 001). J. Infect. Dis. 207(2), 240-247 (2013). A novel replication-deficient recombinant adenovirus serotype 26 vector expressing the envelope protein of a clade A HIV type 1 was evaluated in a group of 60 healthy human volunteers. Three different doses of the recombinant adenovirus vector were used to assess its safety and immunogenicity. The vaccine was found to be generally safe, with no vaccine-related serious adverse events. Although all vaccinated subjects developed neutralizing antibodies against the adenovirus 26 vector, these antibodies did not interfere with the boosting of immune responses against the expressed HIV envelope protein. HIV envelope-specific binding antibodies as well as cellular immune responses were detected in the majority of individuals, persisting for at least 1 year. These results are discussed in the context of previously published protection data in nonhuman primates and of recently published immunological findings with this new vector. Options to proceed to vaccine efficacy trials with this vaccine are reviewed.
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http://dx.doi.org/10.1586/erv.13.26DOI Listing
May 2013

What Has 30 Years of HIV Vaccine Research Taught Us?

Authors:
José Esparza

Vaccines (Basel) 2013 Oct 30;1(4):513-26. Epub 2013 Oct 30.

Bill & Melinda Gates Foundation, PO Box 23350, Seattle, WA 98102, USA.

When HIV was discovered and established as the cause of AIDS in 1983-1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve that goal, different scientific paradigms have been explored. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. Major lessons learned are: the development of an HIV vaccine is an extremely difficult challenge; the temptation of just following the fashion should be avoided; clinical trials are critical, especially large-scale efficacy trials; HIV vaccine research will require long-term commitment; and sustainable collaborations are needed to accelerate the development of an HIV vaccine. Concrete actions must be implemented with the sense of urgency imposed by the severity of the AIDS epidemic.
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http://dx.doi.org/10.3390/vaccines1040513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494212PMC
October 2013

A tale of two vaccines: lessons from polio that could inform the development of an HIV vaccine.

Authors:
José Esparza

AIDS 2013 Jan;27(1):1-5

Global Health Program, Bill & Melinda Gates Foundation, 500 5th Street North, Seattle, WA 98109, USA.

Two vaccine trials that were conducted 50 years apart are reviewed and compared: the 1954 field trial of the Salk inactivated polio vaccine and the RV144 HIV vaccine trial conducted in Thailand between 2003 and 2009. Despite the obvious differences in science and historical periods, several lessons were identified that could inform the future HIV vaccine effort. Those lessons are related to paradigm changes that occur when science progresses, the need to test scientific hypothesis in efficacy trials, the controversies surrounding those trials, the need for strong community and political support, the participation of government and nongovernment institutions, the balance between implementation of other preventive and therapeutic interventions, and the priority given by society to develop a vaccine. If we have the humility and courage to apply some of those lessons, we may be able accelerate the development of an urgently needed HIV vaccine.
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http://dx.doi.org/10.1097/QAD.0b013e328359f2c1DOI Listing
January 2013

Solid vaccine protection against SIV in rhesus monkeys provides proof-of-concept for further evaluation of a novel HIV vaccine approach in humans.

Authors:
José Esparza

Expert Rev Vaccines 2012 May;11(5):539-42

Bill & Melinda Gates Foundation, PO Box 23350, Seattle, WA 98102, USA.

Protection against acquisition of fully heterologous, neutralization-resistant SIV was achieved in rhesus monkeys with adenovirus/poxvirus vector-based vaccines. Protection against acquisition of infection required the inclusion of envelope antigens and correlated with the induction of binding antibodies against the Env protein. The vaccines also facilitate virological control in vaccinated animals that became infected, correlating with multiple humoral and cell-mediated immune responses, especially against the Gag protein. These results are discussed in the context of human trials, particularly the Thai RV144 efficacy trial.
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http://dx.doi.org/10.1586/erv.12.21DOI Listing
May 2012

Understanding the efficacy variables of an HIV vaccine trial.

Authors:
José Esparza

Lancet Infect Dis 2012 Jul 30;12(7):499-500. Epub 2012 May 30.

Global Health Program, Bill and Melinda Gates Foundation, Seattle, WA 98102, USA.

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http://dx.doi.org/10.1016/S1473-3099(12)70117-2DOI Listing
July 2012

Accelerating the development of an AIDS vaccine: the AIDS vaccine for Asia Network (Avan).

Southeast Asian J Trop Med Public Health 2011 Sep;42(5):1130-46

Faculty of Tropical Medicine, Mahidol University, Bangkok.

HIV/AIDS is a major public health problem worldwide, especially in developing countries. The development of a safe and effective HIV vaccine is central to stopping the epidemic and would be a great public health tool. The AIDS Vaccine for Asia Network (AVAN) is a group of concerned investigators committed to assisting regional and global HIV vaccine efforts. AVAN's focus on improving the coordination and harmonization of research, ethical reviews, clinical trial capacity, regulatory frameworks, vaccine manufacturing, community participation, and government advocacy could help accelerate HIV vaccine efforts in the region. At a meeting in November 2010, researchers from various countries in Asia presented their progress in HIV vaccine research and development. Six working groups discussed the current status, gaps and methods to strengthen capacity and infrastructure in various areas related to AIDS vaccine research and development. These discussions led to the development of prioritized action plans for the next 5 years. This report describes the gaps and challenges HIV vaccine research faces in the region and recommends improvement and standardization of facilities, and coordination and harmonization of all activities related to AIDS vaccine research and development, including possible technology transfer when a vaccine becomes available.
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September 2011

The potential global market size and public health value of an HIV-1 vaccine in a complex global market.

Vaccine 2010 Jul 14;28(30):4786-97. Epub 2010 May 14.

Applied Strategies Consulting, San Mateo, CA, USA.

An effective HIV vaccine will be essential for the control of the HIV pandemic. This study evaluated the potential global market size and value of a hypothetical HIV vaccine and considered clade diversity, disease burden, partial prevention of acquisition, impact of a reduction in viral load resulting in a decrease in transmission and delay to treatment, health care system differences regarding access, and HIV screening and vaccination, across all public and private markets. Vaccine product profiles varied from a vaccine that would have no effect on preventing infection to a vaccine that would effectively prevent infection and reduce viral load. High disease burden countries (HDBC; HIV prevalence > or = 1%) were assumed to routinely vaccinate pre-sexually active adolescents (10 years old), whereas low disease burden countries (LDBC; HIV prevalence rate <1%) were assumed to routinely vaccinate higher risk populations only. At steady state, routine vaccination demand for vaccines that would prevent infection only was 22-61 million annual doses with a potential market value of $210 million to $2.7 billion, depending on the vaccine product profile. If one-time catch-up campaigns were included (11-14 years old for HDBC and higher risk groups for LDBC), the additional cumulative approximately 70-237 million doses were needed over a 10-year period with a potential market value of approximately $695 million to $13.4 billion, depending on the vaccine product profile. Market size and value varied across market segments with the majority of the value in high income countries and the majority of the demand in low income countries. However, the value of the potential market in low income countries is still significant with up to $550 million annually for routine vaccination only and up to $1.7 billion for a one-time only catch-up campaign in 11-14 years old. In the most detail to date, this study evaluated market size and value of a potential multi-clade HIV vaccine, accounting for differences in disease burden, product profile and health care complexities. These findings provide donors and suppliers highly credible new data to consider in their continued efforts to develop an HIV-1 vaccine to address the worldwide disease burden.
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http://dx.doi.org/10.1016/j.vaccine.2010.04.098DOI Listing
July 2010

Role of deferoxamine on enzymatic stress markers in an animal model of Alzheimer's disease after chronic aluminum exposure.

Biol Trace Elem Res 2011 Jun 9;141(1-3):232-45. Epub 2010 May 9.

Laboratory of Toxicology and Environmental Health, IISPV, School of Medicine Universitat Rovira i Virgili, Catalonia, Spain.

The effect of the chelator deferoxamine (DFO) on the activity of enzymatic stress markers was assessed in amyloid beta peptide (AβPP) transgenic mice, an animal model of Alzheimer's disease, after oral aluminum (Al) exposure for 6 months. AβPP transgenic (Tg2576) and C57BL6/SJL wild-type mice of 5 months of age were fed a diet supplemented with Al lactate (1 mg of Al/g food). Four groups of Tg2576 and wild-type animals were used: control, Al only, DFO only, and Al plus DFO. Mice in the DFO-treated groups received also subcutaneous injections of 0.20 mmol/kg/d of this chelating agent twice a week until the end of the study at 11 months of age. The hippocampus, cerebellum, and cortex were removed and processed to examine a number of oxidative stress markers. Furthermore, the expression of Cu-Zn superoxide dismutase, glutathione reductase, and catalase was evaluated by quantitative reverse transcriptase polymerase chain reaction analysis. Aluminum levels in the hippocampus of Tg2576 mice were higher than those found in cerebellum and cortex, while the main oxidative effects were evidenced in the presence of DFO only. Oral Al exposure of AβPP transgenic mice would have some potential to promote pro-oxidant events, while DFO administration would not help in preventing these deleterious effects.
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http://dx.doi.org/10.1007/s12011-010-8715-0DOI Listing
June 2011

Protective role of melatonin on oxidative stress status and RNA expression in cerebral cortex and cerebellum of AbetaPP transgenic mice after chronic exposure to aluminum.

Biol Trace Elem Res 2010 Jun 13;135(1-3):220-32. Epub 2009 Aug 13.

Laboratory of Toxicology and Environmental Health, IISPV, School of Medicine, Rovira i Virgili University, Sant Llorens 21, 43201 Reus, Catalonia, Spain.

Aluminum (Al) has been associated with pro-oxidant effects, as well as with various serious neurodegenerative diseases such as Alzheimer's disease (AD). On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, 5-month-old AssPP female transgenic (Tg2576) (Tg) and wild-type mice were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Concurrently, animals received oral Mel (10 mg/kg) until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al + Mel. At the end of the treatment period, cortex and cerebellum were removed and processed to examine the following oxidative stress markers: reduced glutathione, oxidized glutathione, cytosolic Cu-Zn superoxide dismutase (SOD1), glutathione reductase (GR), glutathione peroxidase, catalase (CAT), and thiobarbituric acid reactive substances. Moreover, the gene expression of SOD1, GR, and CAT was evaluated by real-time RT-PCR. The biochemical changes observed in cortex and cerebellum suggest that Al acted as a pro-oxidant agent. Melatonin exerted an antioxidant action by increasing the mRNA levels of the enzymes SOD1, CAT, and GR evaluated in presence of Al and Mel, independently on the animal model.
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http://dx.doi.org/10.1007/s12011-009-8490-yDOI Listing
June 2010

Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum.

Hippocampus 2010 Jan;20(1):218-25

Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Rovira i Virgili University, Sant Llorenç 21, Reus, Catalonia, Spain.

It is well established that aluminum (Al) is a neurotoxic agent that induces the production of free radicals in brain. Accumulation of free radicals may cause degenerative events of aging such as Alzheimer's disease. On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, AbetaPP female transgenic (Tg2576) (Tg) and wild-type mice (5 months of age) were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg) dissolved in tap water until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was removed and processed to examine the following oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of Cu-ZnSOD, GR, and CAT was evaluated by real-time RT-PCR. Aluminum concentration in hippocampus was also determined. The biochemical changes observed in this tissue suggest that Al acts as a pro-oxidant agent. Melatonin exerts an antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD, CAT, and GR evaluated in presence of Al and Mel, with independence of the animal model.
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http://dx.doi.org/10.1002/hipo.20612DOI Listing
January 2010