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Infectious diseases continue to pose significant global health challenges, with emerging and reemerging pathogens threatening public health systems worldwide. At Protheragen, we have dedicated years to pioneering and refining comprehensive solutions in vaccine and therapeutic development, recognizing that the battle against pathogens demands a multifaceted, scientifically rigorous, and proactive approach.

Overview of Infectious Disease Vaccine and Therapeutic Development

Infectious diseases have been a persistent threat to human health throughout history. The development of vaccines and therapeutics is a crucial line of defense against these diseases. Vaccines work by stimulating the immune system to recognize and fight off specific pathogens. They typically contain weakened or inactivated forms of the pathogen, or parts of the pathogen such as proteins or sugars, which trigger an immune response without causing the disease. This immune response includes the production of antibodies that can neutralize the pathogen if it is encountered in the future. Therapeutics, on the other hand, are used to treat individuals who have already been infected. They can work in various ways, such as inhibiting the replication of the pathogen, boosting the immune system's ability to fight the infection, or alleviating symptoms.

An overview of the history of viral outbreaks in the 21st century.Fig.1 Historic overview of the twenty-first-century viral outbreaks. (Meganck R. M., et al., 2021)

Emerging and Re-emerging Infectious Diseases

The 21st century has witnessed a surge in the emergence and re-emergence of infectious diseases, posing significant challenges to global health. Pathogens such as SARS-CoV-2, responsible for the COVID-19 pandemic, and the Zika virus, which caused widespread concern due to its association with birth defects, highlight the need for rapid and effective responses. Other notable examples include the Ebola virus, which has caused multiple outbreaks in Africa, and various strains of influenza, which continue to evolve and evade existing vaccines. These diseases underscore the importance of proactive strategies in vaccine and therapeutic development, ensuring that we are prepared for future outbreaks.

Table 1. Partial list of emerging viral infectious diseases from 1900 to 2020. (Excler J. L., et al., 2021)

Name Year of first description Deaths Comments
'Spanish influenza' 1918 In the range of about 50 million to 100 million 1918: H1N1; other pandemics in 1957–1958 (H2N2), 1968 (H3N2) and 2009 (H1N1)
Rift Valley Fever 1931 Overall CFR < 1%; ~50% for hemorrhagic fever Contact with blood or organs of infected animals and mosquito-borne; several outbreaks in 1977, 1997–1998, 2000–2016
West Nile fever 1937 CFR ~5% Mosquito-borne; worldwide outbreaks (most recent 1999–2010, USA)
Marburg hemorrhagic fever 1967 ~470; very high CFR (24–88%, WHO) Contact with African green monkey; numerous outbreaks in Africa 1969–2018
Lassa fever 1969 ~5,000 deaths annually; CFR 1–2%; Nigerian CFR 25% Contact with rodents or contaminated food or items, mostly in West Africa (Nigeria, 2018)
Acute hemorrhagic conjunctivitis 1969 Rare First identified in 1969; pandemic in 1981; frequent outbreaks worldwide
Ebola hemorrhagic fever 1976–2020 >15,000; CFR 75% First identified in 1976; first major outbreak in 2013–2016 in West Africa and in 2018 in the Democratic Republic of Congo; 29 regional epidemics in 2020 in West and Central Africa
HIV/AIDS 1981 ~37 million Ongoing pandemic
Avian flu 1996 High CFR (60%) H5N1 and H7N9 viruses from poultry; several outbreaks worldwide; the last outbreak in China in 2018
Nipah fever 1999 <1,000? very high CFR Outbreaks in Malaysia, Singapore, Bangladesh, and India
SARS 2002 813; CFR ~ 10% Contained—did not turn into a pandemic
H1N1; H7N9 'swine flu' 2009 284,000; CFR 2.9–9% Pandemic
MERS 2012 935; CFR 34.4% Major outbreak in 2012–2019; ongoing (camels, humans); detected in 27 countries, but mostly in Middle Eastern countries
Chikungunya 2014 Rare Mosquito-borne
Zika 2015 Unknown Mosquito-borne
COVID-19 (SARS-CoV-2) 2019–ongoing >2.3 million; CFR 2–10%; high in elderly and individuals with comorbidities Pandemic—animal-to-animal, animal-to-human and human-to-human transmission

CFR, case-fatality rate.

Animal Models for Infectious Disease Vaccine and Therapeutic Development

Standard Inbred Mouse Strains

Standard inbred mouse strains, such as C57BL/6 and BALB/c, are widely used in infectious disease research due to their genetic homogeneity and well-characterized immune responses. These strains allow for controlled and reproducible studies, enabling researchers to investigate pathogen tropism, replication kinetics, and the efficacy of potential vaccines and therapeutics. Protheragen utilizes these models to conduct rigorous preclinical testing, ensuring that our interventions are effective and safe before advancing to clinical trials.

Immunodeficient Mouse Models

Immunodeficient mice, including SCID and RAG-1 knockout strains, are essential for studying viruses that do not efficiently replicate in standard mouse models. These models enable researchers to investigate the pathogenesis of viruses such as human norovirus and Zika virus, which typically require a human immune system to replicate effectively. Protheragen employs these advanced models to develop targeted therapies that can effectively combat these challenging pathogens.

Genetically Humanized or Human Tissue Xenografted Mice

Genetically humanized mice and human tissue xenografted models provide unique opportunities to study human-specific pathogens and immune responses. These models are particularly useful for viruses like MERS-CoV and HIV, where human-specific receptors and immune responses are critical. Protheragen leverages these advanced models to develop vaccines and therapeutics that closely mimic the human immune response, ensuring greater efficacy and safety.

Collaborative Cross Genetic Reference Population

The Collaborative Cross (CC) is a panel of recombinant inbred mouse strains designed to model human genetic diversity. This population allows for the identification of polymorphic host genes that contribute to phenotypic variation and disease susceptibility. Protheragen utilizes the CC to develop new disease models and to identify genetic factors that influence pathogen susceptibility and therapeutic response.

Our Services

Protheragen offers a comprehensive suite of services designed to accelerate the development of vaccines and therapeutics for infectious diseases. Our services are tailored to meet the unique needs of each project, ensuring that our clients receive the highest quality support at every stage of the development process.

Protheragen is dedicated to advancing the field of infectious disease research through innovative and comprehensive services. Our commitment to excellence and our focus on cutting-edge technologies ensure that we are well-positioned to meet the challenges posed by emerging and re-emerging pathogens. If you are interested in our services, please feel free to contact us.

References

  1. Meganck, Rita M., and Ralph S. Baric. "Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases." Nature medicine 27.3 (2021): 401-410.
  2. Excler, Jean-Louis, et al. "Vaccine development for emerging Services." Nature medicine 27.4 (2021): 591-600.
  3. Sarkar, Sanjay, and Mark T. Heise. "Mouse models as resources for studying infectious diseases." Clinical therapeutics 41.10 (2019): 1912-1922.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.