Antibody Therapy: Past, Present and Future

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Moitra D ◽  
◽  
Miraclin Prasanna A ◽  
Gul N ◽  
Sen P ◽  
...  

The emergence of pandemics like SARS-CoV-2 and a gradual increase in Multidrug Resistant (MDR) infections highlights the need of innovation in therapeutics. Antibodies are one of the potential solutions for long. Antibody therapy has come very long way from the fight against infectious diseases, bacterial toxins to hybridoma technology and monoclonal antibodies. Hybridoma cells receive a deserving attention due to their antigen-specificity. But, as they were murine in origin, Human Anti Murine Antibody (HAMA) emerged. To achieve this, phage display was introduced. The emergence of molecular cloning lead to the generation of genetically engineered recombinant antibodies such as Fab, Fc, Variable Fragment (Fv), Single Chain Variable Fragments (scFv), single domain antibodies, diabodies; like scFv fragments to different moieties, such as drugs toxins, radionuclides, liposomes or quantum dots etc. Minimized antibodies have several advantages like rapid blood clearance, reduced immunogenicity, low retention time in non-target tissues, access to cryptic epitopes facilitating tumor penetration, rapid growth facilitating higher yield and lower production cost. This paper gives an overview of the history of development of antibodies and its fragments as potential therapeutic agents for the treatment of infectious diseases, one of the biggest challenges of humanity.

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
Michael J. Joyner

ABSTRACT Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


1998 ◽  
Vol 64 (7) ◽  
pp. 2490-2496 ◽  
Author(s):  
Kai Koo ◽  
Peggy M. Foegeding ◽  
Harold E. Swaisgood

ABSTRACT The variable-region genes of monoclonal antibody againstBacillus cereus spores were cloned from mouse hybridoma cells by reverse transcription-PCR. The heavy- and light-chain variable-region genes were connected by a 45-base linker DNA to allow folding of the fusion protein into a functional tertiary structure. For detection of protein expression, a 10-amino-acid strep tag (biotin-like peptide) was attached to the C terminus of recombinant antibody as the reporter peptide. The single-chain antibody construct was inserted into the expression vector and expressed in Escherichia coliunder the control of the T7 RNA polymerase-T7 promoter expression system. The expressed single-chain antibody was detected on Western blots by using a streptavidin-conjugated enzyme system. This small recombinant antibody fragment (ca. 28,000 Da by calculation) hadB. cereus spore binding ability and antigen specificity similar to those of its parent native monoclonal antibody.


Author(s):  
Petr Ilyin

Especially dangerous infections (EDIs) belong to the conditionally labelled group of infectious diseases that pose an exceptional epidemic threat. They are highly contagious, rapidly spreading and capable of affecting wide sections of the population in the shortest possible time, they are characterized by the severity of clinical symptoms and high mortality rates. At the present stage, the term "especially dangerous infections" is used only in the territory of the countries of the former USSR, all over the world this concept is defined as "infectious diseases that pose an extreme threat to public health on an international scale." Over the entire history of human development, more people have died as a result of epidemics and pandemics than in all wars combined. The list of especially dangerous infections and measures to prevent their spread were fixed in the International Health Regulations (IHR), adopted at the 22nd session of the WHO's World Health Assembly on July 26, 1969. In 1970, at the 23rd session of the WHO's Assembly, typhus and relapsing fever were excluded from the list of quarantine infections. As amended in 1981, the list included only three diseases represented by plague, cholera and anthrax. However, now annual additions of new infections endemic to different parts of the earth to this list take place. To date, the World Health Organization (WHO) has already included more than 100 diseases in the list of especially dangerous infections.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2219
Author(s):  
George Cosmin Nadăș ◽  
Cristiana Ștefania Novac ◽  
Ioana Adriana Matei ◽  
Cosmina Maria Bouari ◽  
Zoltan Miklos Gal ◽  
...  

The conjunctival bacterial resident and opportunistic flora of dogs may represent a major source of dissemination of pathogens throughout the environment or to other animals and humans. Nevertheless, contamination with bacteria from external sources is common. In this context, the study of the antimicrobial resistance (AMR) pattern may represent an indicator of multidrug resistant (MDR) strains exchange. The present study was focused on a single predisposed breed—Saint Bernard. The evaluated animals were healthy, but about half had a history of ocular disease/treatment. The swabs collected from conjunctival sacs were evaluated by conventional microbiological cultivation and antimicrobial susceptibility testing (AST). The most prevalent Gram-positive was Staphylococcus spp.; regardless of the history, while Gram-negative was Pseudomonas spp.; exclusively from dogs with a history of ocular disease/treatment. Other identified genera were represented by Bacillus, Streptococcus, Trueperella, Aeromonas and Neisseria. The obtained results suggest a possible association between the presence of mixed flora and a history of ocular disease/treatment. A high AMR was generally observed (90%) in all isolates, especially for kanamycin, doxycycline, chloramphenicol and penicillin. MDR was recorded in Staphylococcus spp. and Pseudomonas spp. This result together with a well-known zoonotic potential may suggest an exchange of these strains within animal human populations and the environment.


2017 ◽  
Vol 51 (0) ◽  
Author(s):  
Geisa Fregona ◽  
Lorrayne Belique Cosme ◽  
Cláudia Maria Marques Moreira ◽  
José Luis Bussular ◽  
Valdério do Valle Dettoni ◽  
...  

ABSTRACT OBJECTIVE To analyze the prevalence and factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil. METHODS This is a cross-sectional study of cases of tuberculosis tested for first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espírito Santo between 2002 and 2012. We have used laboratory data and registration of cases of tuberculosis – from the Sistema Nacional de Agravos de Notificação and Sistema para Tratamentos Especiais de Tuberculose. Individuals have been classified as resistant and non-resistant and compared in relation to the sociodemographic, clinical, and epidemiological variables. Some variables have been included in a logistic regression model to establish the factors associated with resistance. RESULTS In the study period, 1,669 individuals underwent anti-tuberculosis drug susceptibility testing. Of these individuals, 10.6% showed resistance to any anti-tuberculosis drug. The rate of multidrug resistance observed, that is, to rifampicin and isoniazid, has been 5%. After multiple analysis, we have identified as independent factors associated with resistant tuberculosis: history of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24–14.05) and re-entry after abandonment (OR = 3.91; 95%CI 1.81–8.43)], smoking (OR = 3.93; 95%CI 1.98–7.79), and positive culture for Mycobacterium tuberculosis at the time of notification of the case (OR = 3.22; 95%CI 1.15–8.99). CONCLUSIONS The partnership between tuberculosis control programs and health teams working in the network of Primary Health Care needs to be strengthened. This would allow the identification and monitoring of individuals with a history of previous treatment of tuberculosis and smoking. Moreover, the expansion of the offer of the culture of tuberculosis and anti-tuberculosis drug susceptibility testing would provide greater diagnostic capacity for the resistant types in Espírito Santo.


2021 ◽  
Vol 13 (5) ◽  
pp. 2694
Author(s):  
Heehyeon Jeong ◽  
Jungyeol Hong ◽  
Dongjoo Park

The outbreak of African swine fever virus has raised global concerns regarding epidemic livestock diseases. Therefore, various studies have attempted to prevent and monitor epidemic livestock diseases. Most of them have emphasized that integrated studies between the public health and transportation engineering are essential to prevent the livestock disease spread. However, it has been difficult to obtain big data related to the mobility of livestock-related vehicles. Thus, it is challenging to conduct research that comprehensively considers cargo vehicles’ movement carrying livestock and the spread of livestock infectious diseases. This study developed the framework for integrating the digital tachograph data (DTG) and trucks’ visit history of livestock facility data. The DTG data include commercial trucks’ coordinate information, but it excludes actual livestock-related vehicle trajectories such as freight types and facility visit history. Therefore, the integrated database we developed can be used as a significant resource for preventing the spread of livestock epidemics by pre-monitoring livestock transport vehicles’ movements. In future studies, epidemiological research on infectious diseases and livestock species will be able to conduct through the derived integrating database. Furthermore, the indicators of the spread of infectious diseases could be suggested based on both microscopic and macroscopic roadway networks to manage livestock epidemics.


PEDIATRICS ◽  
1990 ◽  
Vol 86 (1) ◽  
pp. 65-70 ◽  
Author(s):  
H. Smolders-de Haas ◽  
J. Neuvel ◽  
B. Schmand ◽  
p. E. Treffers ◽  
J. G. Koppe ◽  
...  

Potential side effects of antenatal administration of corticosteroids to prevent neonatal respiratory distress syndrome were studied in 10- to 12-year-old children whose mothers had participated in a randomized, double-blind, placebo-controlled trial of betamethasone. The children had a general physical examination; parents were interviewed about the medical history of their child with special attention to infectious diseases; growth data were collected; and a developmental neurological examination, an ophthalmological examination, and a lung function test were conducted. In the corticosteroid group significantly more hospital admissions because of infectious diseases during the first years of life were reported. On the other variables no differences between the corticoid and the placebo groups were found.


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