A summary of landmark achievements in the development of HIV vaccine and future prospects

1. HIV VACCINES
Development and Challenges
By
YAHAYA FATIHU
B. Pharm, MPSN

2. OUTLINES
• INTRODUCTION
• EPIDEMIOLOGY
• MANAGEMENT
• EVOLUTION OF HIV VACCINES
• CHALLENGES TO VACCINE DEVELOPMENT
• CONCLUSION
• REFRENCES

3. INTRODUCTION
• Human Immunodeficiency
Virus (HIV), a deadly
retrovirus was discovered in
the 1980s.
• Retroviruses are a family of
RNA viruses capable of
making a complementary
DNA copy of viral RNA.
• There were early attempts
as far back ‘80s to develop
HIV vaccine.

4. INTRODUCTION
• Traditional vaccine
formulation methods, e.g.
live and inactivated
pathogens, are not suitable
in the case of HIV infection.
• More than 250 HIV vaccine
clinical trials have been
carried out mainly in the
USA, Africa and Thailand.
(Ng’uni et al., 2020)

5. EPIDEMIOLOGY
• Since the HIV epidemic started, 34.7 million
people have passed away from an AIDS-related
illness.
• 37.6 million individuals were living with HIV
infections in 2020, and 1.5 million new HIV
infections were reported during that time.
• An estimated 85% of HIV cases are spread
through sexual activity.
• While mother-to-child transmission and blood
transfusions are other major means of
transmission
(Picture credit: KFF based on UNAIDS, AIDSinfo)

7. MANAGEMENT
Highly Effective
Combination Antiretroviral
Therapy (HAART) was
introduced In 1996 and has
been The Mainstay
Treatment for HIV ever
since.
(Hargrave et al., 2021)

8. EVOLUTION OF HIV VACCINES
1. RECOMBINANT PROTEINS
2. NOVEL VIRAL VECTORS
3. PRIME BOOST
4. CD8+ T-CELLS INDUCING VECTORS
5. PASSIVE IMMUNIZATION
6. PrEPVACC
7. MESSENGER RNA

9. RECOMBINANT PROTEINS
• HIV Vaccines designed based on this method targeted gp120 or
gp160 HIV-1 envelope proteins
• First HIV vaccines in the 80s such as the VaxSyn (rpg160) and
HIVAC-1e are both recombinant envelope proteins
• They produced transient to mild T-cell responses but no
antibodies were produced against HIV infection

10. NOVEL VIRAL VECTORS
• Novel vector vaccines such as the ALVAC-vector HIV vaccines were
developed in the 90s
• They expressed either gp160 or 120 protein and significantly primed
neutralizing antibody response of proteins.
• Several other vectors (vCP205, vCP300) went through trial and
notably, vCP1521 was the prime in the RV144 trial
• Newer vectors such as the mosaic and CMV vectors may be very
useful in subsequent trials

11. PRIME-BOOST
• This heterologous vaccine approach utilized the novel vectors as
Prime and a bivalent glycoprotein (AIDVAX) as Boost
• As a result, the humoral and cellular immune responses are
enhanced, and neutralizing antibodies are also produced.
• The vaccine effectiveness of RV144, which was created as a prime-
boost, was 60% at 12 months and 31% at 3.5 years.
• Efficacy continues to drop as the number of years increases

12. CD8+ T-CELLS INDUCING VECTORS
• Early in the new millennium, scientists began concentrating on how to utilize a
viral vector to generate CD8+ T-cell activation.
• Inducing a CD8+ T cell response had the dual purposes of therapeutically
controlling post-infection viremia and possibly preventing HIV acquisition.
• The vaccine creates HIV proteins using a recombinant vector containing HIV
genes that are then delivered to the immune system through the Class I antigen-
presenting pathway.
• STEP/HVTN 502 (2004-2007) trial use this approach but the trial was
prematurely terminated after a report of no efficacy amid other concerns

13. PASSIVE IMMUNIZATION
• The discovery of broadly Neutralizing Antibodies (bNABs) against
HIV infection gave rise to a new hope
• bNABs identified (e.g. PG9, PG16, VRC01) reduced viremia and
viral rebound in HIV patients who cease ART treatment
• The biologics bNABs are costly and passive immunization has not
been shown to prevent HIV acquisition.
NB; Active immunity rather than passive is far more desirable in HIV
infection

14. PrEPVacc
• Tenofovir-containing vaginal gel combined with vaccine
produces high efficacy (81%) in an animal model
• The effectiveness of PrEP also lead researchers to think of
combining antiretrovirals with vaccines
• A trial using a combination of two vaccine regimens and Prep
(PrEPVacc) is ongoing and results are expected soon

15. MESSENGER RNA
Major Pharmaceutical companies e.g. Moderna and Pfizer have successfully produced
a number of mRNA Vaccines like COVID, Influenza and Zika virus vaccines.

16. mRNA VACCINE:
Major Milestones
• 2000s: Molecular biology and bioinformatics techniques rapidly evolved and led to the
HIV genome sequencing and cloning
• 2020: COVID-19 Pandemic and testing of mRNA Technology
• Late 2020: Successful launch of Pfizer and Moderna COVID-19 mRNA vaccines
• Early 2021: First Phase 1 clinical trial of an mRNA-based HIV vaccine, IAVI G001
• Sept 2021: A similar phase 1 clinical trial, IAVI G002
• Jan 2022: Moderna announced;
“In a proof-of-concept trial last year, the research team found the HIV antigens produced the desired
immune response in 97% of participants”.

17. MODERNA mRNA VACCINE
• Researchers administered participants in IAVI G001 two doses of the eOD-GT8 60mer vaccination
or a placebo.
• The eOD aspect of this nanoparticle-mRNA vaccine is an engineered outer domain of the Env
gp120 that binds to CD4.
• The vaccine's eOD design specifically targets germline B cells and aids in their development into
bNAB.
• Initial findings showed that 97% of subjects who received the eOD-GT8 60mer vaccine developed
VRC01-class IgG B cells.

18. CHALLENGES TO
VACCINE
DEVELOPMENT
• REGULATORY
• BIOLOGICAL
• FINANCIAL

19. Desirable Qualities of
an Ideal HIV Vaccines
I. Elicitation of long-
lasting protection.
II. Broadly acting against
HIV subtypes and
variants.
III. Affordable to affected
low-income countries.
IV. Easy to administer and
be stored.
V. Should be therapeutic or
preventative.

20. CHALLENGES TO
VACCINE
DEVELOPMENT
1. Rate of mutation of
HIV
2. Nature of the virus
3. Differing types and
clades of HIV
4. No appropriate
Animal models
5. Limited information
on immunogenicity
BIOLOGICAL

21. CHALLENGES TO VACCINE
DEVELOPMENT Vaccine trials like
HVTN502, HVTN505
and HVTN702 were
prematurely terminated
because they were
slightly more cases of
HIV infections in
vaccine recipient
groups than in those
groups treated with a
placebo
(Ng’uni et al., 2020)
REGULATORY
There are reasonable ethical concerns regarding
the approval of HIV Vaccine human trials due to
unusual occurrences that surrounds earlier
vaccines and trials

22. CHALLENGES TO VACCINE
DEVELOPMENT
While 90% of HIV
infection occur in
developing countries,
85% of HIV research
funding comes from
USA and Bill & Melinda
Gates Foundation
approximately $680
million (Hargrave et al.,
2021)
FINANCIAL
There is a gap between the resources and funding
needed to develop an effective vaccine and the
countries that have high rates of HIV infections

23. CONCLUSION
HIV vaccine development is becoming a
reality despite years of challenges. Continuous
efforts are needed in this aspect to put an end
to the HIV epidemic.

24. REFERENCE
S
• Hargrave, A., Mustafa, A. S., Hanif, A.,
Tunio, J. H., & Hanif, S. N. M. (2021).
Current Status of HIV-1
Vaccines. Vaccines, 9(9), 1026.
https://doi.org/10.3390/vaccines9091026
• Khalid, K., Padda, J., Khedr, A., Ismail, D.,
Zubair, U., Al-Ewaidat, O. A., Padda, S.,
Cooper, A. C., & Jean-Charles, G. (2021).
HIV and Messenger RNA (mRNA)
Vaccine. Cureus, 13(7), e16197.
https://doi.org/10.7759/cureus.16197

25. REFERENCE
S
• Maharjan, P. M., & Choe, S. (2021). Plant-
based COVID-19 vaccines: Current status,
design, and development strategies of
candidate vaccines. Vaccines, 9(9), 992.
https://doi.org/10.3390/vaccines9090992
• Ng’uni T, Chasara C and Ndhlovu ZM
(2020) Major Scientific Hurdles in HIV
Vaccine Development: Historical
Perspective and Future Directions.
Front. Immunol. 11:590780.
doi: 10.3389/fimmu.2020.590780
• https://edition.cnn.com/2022/01/31/health/
moderna-mrna-hiv-vaccine/index.html