At present, scientists are working on biodegradable and biocompatible nano polymers that are used as the delivery systems to trigger both the humoral and the cellular immune responses. These nanoparticles are potent immunomodulators in various types of vaccines which control the release of the antigens and therefore providing the better and higher quality of immune responses. In the field of modern vaccinology, the safety and effectiveness of several nanoparticles and liposomes have been confirmed.

1. POLYMER BASED
NANOADJUVANTS FOR HEPATITIS
C VACCINE
Niti Chowdhury & Shreejit Saha
B. Sc. 2nd year
St. Xavier’s College(Autonomous), Kolkata
Department of Microbiology

2. What are vaccines? What were their
disadvantages?
 The traditional vaccines which have been around ever since 1976 when it was
discovered by Edward Jenner.
 They are a substance which contains a live attenuated version of the micro
organism which causes the particular disease in question.
 The traditional vaccines were effective in inducing the antibody-based immunity,
but highly reactogenic.
 Due to this safer, less reactogenic vaccines were developed. However, this was
achieved with compromised vaccine efficacy.
 To solve this, adjuvants were added to these vaccines.

3. What are adjuvants?
 According to the British Society of Immunology, adjuvants are defined as –
‘substances used in a combination with a specific antigen that produced a more
robust immune response than the antigen alone, thus encompassing a wide range
of materials.’
 The word adjuvant comes from the Latin word: adjuvare which means to help.
 These are substances which when released together with Silver (Ag), enhance the
immune response by the sustained release of Ag (releasing Ag slowly) from
injection site and increase the contact period of Ag with macrophage or other Ag
receptive cells. This is known as the Depot effect of the adjuvant.

4. The adjuvants possess a number of
mechanisms to improve the immunity
which include:
 Increase the immunological half life of the immunized antigens.
 Enhancing the delivery of the immunized antigens to the antigen presenting cells.
 These antigens can be processed by the antigen presenting cells, while triggering
the immunomodulatory cytokines.
 The usage of adjuvant has also allowed for the enhancement of the helper T type I
(Th1) or type II (Th2) immune responses to the vaccine.

5. Common examples of adjuvants:
 Freund’s complete adjuvant consists of heat killed Mycobacterium
tuberculosis in non-metabolizable oils (paraffin oil and mannide monooleate).
It also contains trehalose 6,6 dimycolate. It is an emulsion of water in oil along
with mycobacterial or nocardial Ag.
 Freund’s incomplete adjuvant (1940) is prepared from non-metabolizable
oils (paraffin oil and mannide monooleate). It is an emulsion of water in oil. It
lacks the heat-killed Mycobacterium tuberculosis which makes it less
inflammatory.
 Aluminium adjuvants – Potassium Aluminium Sulphate (Alum), Aluminium
Hydroxide, Aluminium Oxide.

6. What are nanoparticles?
 At present, nano vaccine development is in progress, especially the biodegradable
and biocompatible nano polymers that are used as the delivery systems to trigger
both the humoral and the cellular immune responses.
 These nano particles are potent immunomodulators which control the release of
the antigens and therefore providing the better and higher quality of immune
response.
 It is these specific nano particles which are thus called nano adjuvants.

7. Advantages of Nano adjuvants:

8. Polymer-based nano adjuvants:
 The nanoparticles could potentially serve as vaccine delivery vehicles, functioning
as adjuvants, providing effective antigen delivery.
 This is because the introduction of recognizable molecules on the surface of the
particle gives it the ability to recognize target cells, and also permits the gradual
degradation of the polymer of the particle within the cell.
 Nanoparticles themselves have antigenic or medicinal activity, and thus they can
elicit a strong immune response. Nanomaterials can also inhibit or kill pathogenic
cells using their cellular toxicity or a strong immune response.

9. PLGA in nano technology and vaccine
development
 For several decades, there has been an intense focus on Poly Lactic-co-Glycolic
Acid (PLGA) in the field of nano technology owing to its beneficial properties as a
biodegradable polymer along with its gradual degradation rate before
internalization by the Antigen Presenting Cells.
 The efficacy of the PLGA particles in the production of the viral vaccines have been
confirmed.
 The American Food and Drug Administration (FDA) has approved PLGA for human
and veterinary use and its particles have shown to enhance the efficacy of delivery
while also improving the strength of vaccine formulation.

10. WHAT IS HCV?
 The HCV or Hepatitis C Virus consists of an enveloped glycoprotein. It belongs to
the Flaviviridae family of Viruses.
 Its viral genome is a positive, single stranded RNA. This virus consists of both
enveloped and core proteins.

11. TREATMENT OF HCV
 Although the exact mechanism to inhibit the virus remains unknown, the
administration of the pegylated interferon or ribavirin and interferon is often
applied to supress the replication of the HCV.
 Cirrhosis of the liver may also be delayed by a combination of interferon alfa-2B
and ribavirin.
(Ribavirin is a nucleoside analog and an active guanosine that could inhibit the viral
structure assembly for the prevention of several viruses in – vitro, including
Flaviviridae.)

12. HCV protein and PLGA
 In a research by Roopngam et al. it was observed that the HCV1b-E2 protein was
effectively encapsulated in the PLGA nanoparticles and their use as a delivery
system with adjuvant properties resulted in effective immunomodulatory function.
 These PLGA nanoparticles have had adjuvant function to trigger cell mediated
immune responses by the expression of the cytotoxic T cells.
 The HCV1b-E2-PLGA nanoparticles enhanced cellular immunity.

13. Some more examples of polymer based
nano particles
 However, there are some more types of polymer-based nanomaterials which have come up.
They include:
 Chitosan
 Polylactic acid (PLA)
 Polyglutamic acid (PGA)
 Polyethylenimine (PEI)
 Poly(ethylene glycol) (PEG)

14. What lies ahead?
 Research work on the nanoparticle-based drug delivery systems include:
 the surface modification of the nanoparticles to increase target characteristics
 the detection of the carrier materials to get suitable drug release speeds
 optimizing the preparation of nanoparticles with targeted tissues, organs and blood.
 Currently, research work on nanoparticles is restricted to their physiochemical
properties and toxicity, including: the specific interaction of nanoparticles with the
cells, tissues, organs and biomolecules in the body and the effect on the body’s
metabolism.

15. References:
 https://www.immunology.org/public-information/bitesized-immunology/vaccines-and-therapeutics/adjuvants-
introduction
 https://www.invivogen.com/cfa
 https://www.invivogen.com/ifa#:~:text=Details-
,IFA%20(Incomplete%20Freund's%20adjuvant)%20is%20one%20of%20the%20most%20commonly,paraffin%20oil%
20and%20mannide%20monooleate).
 Medical Microbiology for Undergraduates – BS Nagoba & Asha Pichare
 Nucleic acids presenting polymer nanomaterials as vaccine adjuvants (Alice Comberlato, Kaltrina Paloja and
Maartje M. C. Bastings)
 Polymer-based nanoadjuvants for hepatitis C vaccine: The perspectives of immunologists (Piyachat Evelyn
Roopngam and Tirawat Wannatung)
 Polymer-Based Nanomaterials and Applications for Vaccines and Drugs (Jinyu Han, Dandan Zhao, Dan Li,
Xiaohua Wang, Zheng Jin and Kai Zhao)
 Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies (Michael Lim, Abu Zayed Md
Badruddoza, Jannatul Firdous, Mohammad Azad, Adnan Mannan, Taslim Ahmed Al-Hilal, Chong-Su Cho
and Mohammad Ariful Islam)

16. Thank you!