May 24, 2024

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Overview of research and development of global infectious disease vaccines

Overview of research and development of global infectious disease vaccines



 

Overview of research and development of global infectious disease vaccines

 

As of January 1, 2023, global vaccine research and development includes a total of 966 candidate vaccines, of which 23% ( 220 ) are traditional inactivated or attenuated vaccines.

Advances in molecular technology have facilitated the development of other platforms, such as recombinant protein vaccines, nucleic acid vaccines, and viral vector vaccines, which further diversify global vaccine R&D.

 

Recombinant protein vaccines accounted for the largest proportion of all pipelines under development, accounting for 22% ( 215 species ), which benefited from their good safety, stability and ease of manufacture.

Nearly 100 candidate recombinant vaccines are in phase I clinical development, currently the largest number of all types.

 

Overview of research and development of global infectious disease vaccines

 

The success of the COVID-19 mRNA vaccine has laid the foundation for the development of nucleic acid vaccines including mRNA and DNA vaccines.

Such vaccines currently rank second in the overall R&D pipeline, accounting for 18% ( 173 ).

Due to the flexibility of such vaccines in developing vaccines against highly variable pathogens, many vaccine candidates are currently in development, including COVID-19 (95 candidates ), influenza ( 24 ) and HIV ( 21 ).

 

Viral vector vaccines have also attracted attention in recent years because of their potential to induce robust and long-lasting immune responses, including adenoviruses, retroviruses, lentiviruses, and poxviruses.

Currently, there are 133 candidate viral vector vaccines in development, in particular, adenoviral vectors ( 82 types ) have been widely used to develop vaccines for diseases such as Ebola, HIV, influenza, and COVID-19.

To circumvent the limitations of preexisting immunity to adenovirus type 5 ( Ad5 ), multiple adenovirus serotypes have been developed, such as Ad26, Ad35, and Ad11.

 

Conjugate vaccines were next at 11%, with 109 vaccine candidates. Conjugate vaccines are often developed against pathogens such as meningococcus, pneumococcus and Haemophilus influenzae.

These vaccines are based on the covalent linkage of immunogenic protein carriers ( mainly tetanus toxoid, diphtheria toxoid, or group B meningococcal outer membrane protein ) to capsular polysaccharides or peptides to enhance immunogenicity and stability.

 

Overview of research and development of global infectious disease vaccines

 

The top three diseases for vaccine development were all caused by viruses: COVID-19 ( 246; 25% ), influenza ( 104; 11% ) and HIV ( 84; 9% ).

In addition to more than 50 vaccines that have received market approval or emergency use authorization for the COVID-19, there are 64 candidate vaccines that have entered the third phase or submitted marketing applications, of which 47% are mRNA vaccines.

In the current pipeline, at least 14 nasal vaccines are in development.

 

The high variability of the HIV viral genome and the high level of glycosylation of the HIV envelope glycoprotein ( gp ) often induce immune evasion, which hinders the development of HIV vaccines.

Currently, it is hoped to stimulate the production of broadly neutralizing antibodies by targeting conserved regions of envelope proteins that vary little between HIV strains, such as gp160, gp41, and gp120.

New vaccines such as viral vectors and mRNA have brought hope for the development of HIV vaccines, and two mRNA vaccines capable of inducing neutralizing antibodies are currently in phase I trials (NCT05001373 ) .

 

Contrary to the dominance of new technologies in HIV vaccine development, 40% of influenza vaccine candidates are inactivated vaccines.

Given the variety of influenza subtypes resulting from antigenic drift, universal vaccines are increasingly being developed to reduce the need for frequent vaccinations.

These vaccines are designed based on highly conserved epitopes in viral hemagglutinin, neuraminidase, or other proteins. Currently, six universal influenza vaccine candidates are in phase 3 clinical trials.

 

In addition to the above three diseases, there are a large number of vaccines against RSV in development ( 31 species ), and a breakthrough was recently made targeting the stable pre-F protein.

Two recombinant protein vaccines, PF-06928316 and GSK3844766A, produced >80% protection in phase III trials and will be approved by the FDA in 2023.

An mRNA vaccine ( mRNA-1345 ), which also demonstrated >80% protection in a Phase III trial, has been granted Breakthrough Therapy designation by the FDA.

 

Non-viral pathogens such as malaria ( 57 species ) and pneumococci ( 40 species ) also represented an important area.

Conjugate vaccines are the main focus for pneumococci, while recombinant proteins and viral vectors are the main platforms for malaria vaccines.

Vaccines for diseases such as Ebola are also being developed, building up strength for future breakthroughs.

 

Overview of research and development of global infectious disease vaccines

 

Currently, vaccine R&D is concentrated in the United States ( 355 ), China ( 271 ) and Western Europe ( 144 ).

These regions have some differences in technology platform preferences: the U.S. pipeline has more nucleic acid vaccines, while China’s pipeline has more inactivated vaccines and the least viral vector vaccines than the U.S.  and Western Europe. Most ( 68% ) of the vaccine candidates were developed independently or in partnership with private companies, while 25% were developed by academic or other nonprofit organizations.

Notably, vaccine candidates against HIV and malaria are primarily being developed by academic or other nonprofit organizations.

 

The success of vaccine development depends largely on the identification of effective antigens and the application of technology platforms. Furthermore, international cooperation and coordinated efforts are essential to achieve these goals.

The COVID-19 pandemic has highlighted the importance of global cooperation in response to public health emergencies and demonstrated the potential benefits of sharing resources and expertise to accelerate vaccine development and deployment.

This includes sharing scientific resources and expertise, collaborating on research and development, and establishing coordinated mechanisms for outbreak preparedness and response.

 

 

 

 

references:

1. The R&D landscape for infectious disease vaccines. Nat Rev Drug Discov. 2023 Jul 20.

Overview of research and development of global infectious disease vaccines

(source:internet, reference only)


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