This document discusses the development of polymer-based nanoadjuvants for a hepatitis C virus (HCV) vaccine. It first provides background on vaccines and adjuvants, describing common adjuvants like Freund's complete adjuvant. It then discusses nanoparticles made from polymers like poly lactic-co-glycolic acid (PLGA), which are biodegradable and can effectively encapsulate antigens. One study showed PLGA nanoparticles encapsulating HCV proteins enhanced cellular immunity in mice. The document notes challenges to an HCV vaccine like genetic diversity between virus strains, but suggests surface-modified polymeric nanoparticles may help optimize drug release and targeting to improve vaccine delivery.

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?
They are a substance which contains a
live attenuated version of the micro
organism which causes the particular
disease in question.
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.’

3. The 3 main steps in the action of Adjuvants:
Image: In vivo Reference: Mechanism of Adjuvants
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.
Step 3:
Step 2:
Step 1:

4. What are Nanoparticles?
De Gruyter: PLGA Nanoparticle

5. PLGA in Nanotechnology and Vaccine
Development:
TEM of PLGA Nanoparticles
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.
ATA Scientific Instruments: Nanoparticles

6. What is Hepatitis C Virus?
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.
• 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.

7. Why do we not have a HCV vaccine?
30% divergence was seen between the 7
genotypes of the HCV.
However, on the other hand, only 8% divergence
was seen between the genotypes of HBV. This
allowed for successful preparation of the HBV
vaccine.
The effective escape strategies cause a very high
rate of chronic hepatitis following acute
infection.

8. 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.

9. What lies ahead?
• Presently, scientists are focussing on three main factors to improve these nano-particle based drug
delivery systems:
o the surface modification of the nanoparticles to increase target characteristics.
o the detection of the carrier materials to get suitable drug release speeds.
o optimizing the preparation of nanoparticles with targeted tissues, organs and blood.
This Photo by Unknown Author is licensed under CC BY-NC

10. References:
• Nucleic acids presenting polymer nanomaterials as vaccine adjuvants (Alice Comberlato, Kaltrina Paloja and Maartje M. C. Bastings)
• Hepatitis C virus E2 protein encapsulation into poly d, l-lactic-co-glycolide microspheres could induce mice cytotoxic T-cell response
(Roopngam et. al.)
• 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)
• Why is it so difficult to develop a hepatitis C virus preventive vaccine (Zingaretti, De Francesco, Abrignani)
• 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%2
0monooleate).
• https://www.researchgate.net/publication/301316328_Cellular_immune_response_to_hepatitis-C-
virus_in_subjects_without_viremia_or_seroconversion_Is_it_important
• Medical Microbiology for Undergraduates – BS Nagoba & Asha Pichare

11. • A special thank you to Father Principal, Dr. Arup Kumar Mitra, Head of
the Department of Microbiology, Professors, all the research scholars
and everyone who have helped us prepare this presentation.