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The Past, Present and Future of Vaccine Adjuvants

Vaccine adjuvants are accredited with assisting to boost the immune response in the host post-vaccination. Immunologists and infectious disease specialists are in covenant over the advantageous uses of adjuvants in vaccines today, particularly as a means to decrease the number of doses, surge the probability of a continuous immunological response and decrease the overall prevalence of disease.The most cost effective and efficient technique for the prevention of diseases caused by infectious pathogens is the administering of vaccines. However, despite the staggering success of vaccines, there is still a requirement for the development of strong and safe vaccines to combat emerging pathogens, re-emerging old pathogens, and also for the improvement of the protection offered by the existing vaccines which are increasingly proving to be inadequate.

One of the most necessary strategies for the production of efficient vaccines is the choice and application of a suitable adjuvant. Immunologic adjuvants are necessary for the enhancement of the potency of the vaccine by improving the cell-mediated immune response to the antigens of vaccines. Therefore, the formulation of vaccines with the application of the right adjuvants is an efficient approach towards the development of long lasting immunity in human beings. It must, however, be noted that only a few adjuvants have been licensed for human use due to concerns relating to their toxicity and safety. This article will have a look at the current knowledge about adjuvants, their characteristics and potential benefits. Adjuvants have varied modes of action and should be chosen based on the requirement of the type of immune response which is desired.

Vaccine Adjuvant Market

Infectious diseases have continued to remain the second highest cause of death globally, preceding cardiovascular diseases. In the case of infants and children, they have become the leading cause of death. This has made the final goal of vaccination to be the generation of a pathogen specific immune response which can provide long lasting immunity against infection. This has become even more important in the light of the recent epidemics of the H1N1 influenza, SARS, and the Ebola virus. Subunit Vaccines, Inactivated Vaccines, and Live-attenuated Vaccines are the three types of vaccines currently used in humans. The majority of the most effective vaccines used are that of the live-attenuated type. These are composed of a bacterium or virus which can replicate within the host. Examples of live-attenuated type include chicken pox, oral polio, rotavirus and yellow fever vaccine. Inactivated Vaccines are the ones which contain heat inactivated or chemically inactivated particles of the pathogen. These vaccines are considered safe but generate a very weak and short lived response of the immune system, which leads to the requirement of the dosage being increased or administered multiple times.

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Adjuvants have been defined as the agents which are added to vaccine formulations and lead to the enhancement of the immunogenicity of antigens and also the induction of protection against infection. Vaccines which have been manufactured from inactivated pathogens or live-attenuated pathogens can elicit a sufficient protective response from the immune system because they contain naturally occurring adjuvants. In comparison, the protein based vaccines have limited immunogenicity even though they are superior in terms of cost efficiency and safety. Adjuvants play a major role in these protein based vaccines as they induce strong and long lasting immune responses, and make the proteins more effective. The recent developments in such cases include the production of protein based vaccines by mixing with aluminum salts (alum). The benefits of the addition of adjuvants include

  • Reduction in the required dosage of the antigen
  • Reduction in the required number of vaccine doses
  • Enhancement of vaccine efficiency in infants, elderly, and immune-compromised people
  • Induction of long lasting and faster immune responses
  • Induction of vigorous cell-mediated immunity
  • Broader protection
  • Facilitation of mucosal immunity
  • Overcoming antigen competition which is resultant in combination vaccines
  • Increasing the functional antibody titer

The end goal of vaccination is the generation of potent and long term immunity against diseases. Adjuvants play an indispensable role in aiding vaccines to achieve their true potential. In the past, vaccine formulations with adjuvants were based on single type adjuvants such as emulsions or alums, but the latest vaccine targets have incorporated well defined CMI (cell mediated immunity), as well as high concentration of antibody.

The following is a list of licensed vaccine adjuvants:

Adjuvant name (year
licensed)
ClassManufacturerDescription
Alum (1926)Mineral SaltVariousImproves Immoral immune responses and antigen stability. Antigens are adsorbed to the surface. The adjuvant in >80% of vaccines licensed for human use.
Th2 type immune responses.
MF59 (1997)Oil-in- water emulsionNovartisImproves humoral and cell-mediated immunity. Used in influenza vaccines.
Antigen delivery.
AS03 (2009)Oil-in- water emulsionGSKImproves Immoral and cell-mediated immunity. Used in influenza vaccine during 2009 H1N1 pandemic
Virosome (2009LiposomeBeam Biotech (cruecell)Improves humoral and cell-mediated immunity. A virosome is the reconstituted membrane of an enveloped virus. The vaccines for influenza and for Hepatitis A are approved products
ASO4 (2005)Alum-adsorbed TLR4 agonist GSKImproves Immoral and cell-mediated immunity Combination of aluminum adjuvant with monophosphoryl lipid A (MPL) co-adsorbed. Used for HPV and HBV vaccine

 

The following are the class of adjuvants known as immune-stimulators, which are in various stages of development:

Adjuvant nameClassDescriptionClinical Phase
CpGTLR 9 agonistEnchances antibody titer, Th1 type immunity and cD8 T cell-mediated immunity. CpG oligonucleotidesPhase 3
FlagellinTLR 5 agonistEnchances antibody titer, Th1 and Th2 type immunity. Flagellin linked to antigenPhase 1
PolyI:CTLR3 agonistEnchances antibody titer, Th1 type immunity and cD8 T cell-mediated immunity. Double-stranded RNA analoguesPhase 1
AS01Combination Enchances antibody titer, Till type immunity and cD8 T cell-mediated immunity. Combined with MPL, QS21 and liposomesPhase 3
AS02Combination Enchances antibody titer and Thl type immunity. Combined with MPL QS21 and emulsionPhase 3
ISCOMs and ISCOMMATRIXCombination Enchances antibody titer, Thl and Th2 type immunity and cD8 T cell-mediated immunity. Combined with saponin and phospholipidPhase 2

 

There has been substantial progress made in the field of adjuvant research in the past two decades, based on which, vaccinologists are now able to choose an appropriate adjuvant from classical adjuvants, immune-stimulants and also their combinations. The availability of the various adjuvants in different combinations is expected to facilitate the rational designing of vaccines against infectious diseases.

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