Watch the slideshow for a better understanding: https://youtu.be/frmGwCEtDnM 1. Learn how mRNA vaccines work. 2. Learn challenges in making HIV vaccines. 3. Learn about the advantage of mRNA vaccines in HIV 4. Learn about trials.

1. Welcome to
JCMI Teleconference
DR. DHRITI GUPTA, DR. VIMALA THAMBI, DR.
HAJARA JOUNDI, DR. KALPANA GIRI, DR.
WARDA HAMEED
CLINICAL EXTERNS, JCMI MEDICAL CENTER, FL
UNDER SUPERVISION OF DR. G. JEAN-CHARLES
JULY 10, 2021

2. Which COVID vaccine
did you take?
WHAT WAS THE TYPE OF VACCINE?

3. mRNA Vaccines and HIV
JCMI TELECONFERENCE
JULY 10, 2021

4. Introduction
Over 37.6 million [30.2–45.0 million] people worldwide living with HIV at the end of 2020
About 690 000 [480 000–1 million] people died from HIV-related causes in 2020 and 1.5 million [1.1–
2.1 million] people were newly infected.
Vaccine: An alternative to lifelong Antiretroviral therapy (ART), a functional cure.
Therapeutic
vaccine
But No
effect in HIV
viral load
Classic
vaccine
Low CD8 T-
cell immune
response

5. Why vaccine is important over Antiretroviral therapy?
People living with HIV
No cure No eradication
 ART can only suppress HIV replication in infected cells.
 It has no impact in latent reservoir.
 Reduction in morbidity and mortality.
 Treatment is lifelong treatment.
 Unable to cure or eradicate the infection.

6. Goals of an HIV vaccine?

7. Why no HIV vaccine yet?

8. Hurdles in developing HIV vaccine.

10. Nucleic acid based vaccines :
Rapid response applications
★ Viral vectors → vector specific immune response (esp on boosting)
★ pDNA → inefficient delivery of pDNA into nucleus of target cells
★ mRNA → do not generate infectious particles or integrate into genome of host cells

12. Why mRNA?
“The mRNA platform makes it easy to develop
vaccines against variants because it just
requires an update to the coding sequences in
the mRNA that code for the variant,” Rajesh
Gandhi, MD, an infectious diseases physician
at Massachusetts General Hospital and chair
of the HIV Medicine Association
Dr. Khalid...?

13. Advantages of mRNA vaccine :
★ Synthetic production
★ Rapid and scalable production
★ Non-infectious, non-integrating,
naturally degraded
★ Stimulate Innate immune response
★ Enhanced Broad T cell and B cell
immune responses

14. Types of mRNA vaccine :
★ Conventional
★ Self amplifying

15. Conventional mRNA vaccine :
ADVANTAGES
★ Shorter RNA length
★ Direct Ag expression from mRNA
★ No risk of anti vector immunity
★ Nucleoside based modification
DISADVANTAGES
★ Shorter duration of expression
★ Higher effective doses needed

16. Self amplifying mRNA vaccine :
ADVANTAGES
★ Enhanced and prolonged Ag expression
★ Lower effective doses
★ Vaccine self amplification→
potential apoptosis of vaccine carrying
cells →
enhanced Cross presentation
DISADVANTAGES
★ Longer RNA length → needs
production of high quality mRNA
★ Self amplification→ elevated
inflammation
★ Interaction b/w nSP and host cells
needs to be studied.

17. Production

18. Potential targets for HIV mRNA vaccine

19. Antigen
targeted
Delivery
methods
Route of
administration
Elicited
Response
s
Model
used
Env (HIV) Nucleoside
modified LNP
Intradermal Humoral,
cellular
Mice,
NHPs
Gag (HIV) Unmodified
cationic
nanomicelles
Subcutaneous Humoral Mice
Gp140 (HIV) Cationic
nanoemulsion
Intramuscular Humoral,
cellular
Mice,
rabbits,
NHPs

20. Pre-requisites for a HIV antibody
•Multiple envelop epitopes
Broad coverage antibody
•Blocks viral entry
Broadly Neutralizing antibody (bnAb)
High titers in the plasma
Long-lasting
CD8+ T cell inducing immunogen

21. Broadly neutralizing Antibodies for HIV-1
prevention:

22. Targets of bnAb:

23. Ongoing mRNA vaccine in HIV
 Scientists have been working toward an HIV cure for
decades, although a vaccine has so far proven elusive.
 Moderna has created an HIV vaccine, working with the
International AIDS Vaccine Initiative (IAVI) and Scripps
Research, that uses mRNA technology in an effort to
generate broadly neutralizing HIV-1 antibodies, or bNAbs,
that act against the virus.
 Results from a phase 1 trial show that the desired
response occurred in 97% of participants who received the
vaccine.

24. Vaccine is here,
NOW WHAT?

25. Challenges in mass
vaccination
1. SUSTAINABILITY OF COLD CHAIN
2. MYTHS ABOUT MRNA VACCINE

27. Sustainability of cold chain
 Different vaccines require different
temperatures.
 Moderna’s vaccine must be stored at -20
degrees Celsius
 Pfizer’s shot that temperature drops to -70 C

28. Myths about mRNA
vaccine.
WHAT DO THINK?

29. Myths about mRNA vaccine...
 HIV vaccines can give people HIV.
 An HIV vaccine already exists.
 Joining an HIV vaccine study is like being
a guinea pig.
 A person must be HIV-positive (infected)
to be in an HIV vaccine study.
 mRNA changes genetic makeup.

30. References:
1. HIV vaccine development - Wikipedia. (2021). Retrieved 10 July 2021, from https://en.wikipedia.org/wiki/HIV_vaccine_development
2. https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(19)30041-3
3. https://www.aidsmap.com/news/mar-2020/hiv-vaccine-generates-broadly-neutralising-antibodies-passes-first-safety-and-proof
4. https://www.genengnews.com/news/mrna-tracking-with-fluorescent-cytosine-preserves-natural-behavior
5. Maruggi G, Zhang C, Li J, Ulmer JB, Yu D. mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases.
Mol Ther. 2019;27(4):757-772. doi:10.1016/j.ymthe.2019.01.020
6. Nurunnabi, Tauhidur & Roy, Bipradas & Sobhani, Mahbub. (2012). Chronic Psychological Stress and AIDS: Biomolecular Mechanisms.
7. Caskey, M., Klein, F., & Nussenzweig, M. (2016). Broadly Neutralizing Antibodies for HIV-1 Prevention or Immunotherapy. New England
Journal Of Medicine, 375(21), 2019-2021. doi: 10.1056/nejmp1613362
8. Mu Z, Haynes BF, Cain DW. HIV mRNA Vaccines-Progress and Future Paths. Vaccines (Basel). 2021;9(2):134. Published 2021 Feb 7.
doi:10.3390/vaccines9020134
9. Esteban I, Pastor-Quiñones C, Usero L, Plana M, García F, Leal L. In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?
Viruses. 2021 Mar 18;13(3):501. doi: 10.3390/v13030501. PMID: 33803790; PMCID: PMC8003302
10. https://www.who.int/news-room/fact-sheets/detail/hiv-aids
11. https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjJ7qroq9jxAhVCzjgGHSHvAWkQFjABegQIHhAD&u
rl=https%3A%2F%2Fwww.contagionlive.com%2Fview%2Fmoderna-unveils-results-of-new-mrna-vaccine-candidate-
trials&usg=AOvVaw0qL6RbSbgR9xuC6YzJ6Nvs
12. https://www.promegaconnections.com/mrna-vaccines-for-covid-19-the-promise-and-
pitfalls/?utm_source=youtube&utm_medium=social&utm_campaign=mRNA%20vaccine%20video&utm_term=description

31. Thank You.
“COVID-19 showed us what we can do if we want to move a vaccine forward quickly”
Andrew Pekosz, PhD, Virologists

32. In the near FUTURE
LET’S HOPE!

33. New HIV Vaccine in the market