This document provides an overview of HIV vaccine development. It discusses the challenges of developing an HIV vaccine, including the high mutation rate of the virus and lack of appropriate animal models. The document outlines the main approaches to HIV vaccine development, including generating neutralizing antibodies, activating CD8+ T cells through viral vectors, and using prime-boost approaches. It also describes the structure and life cycle of HIV, the disease burden, and immune responses important for a vaccine, such as broadly neutralizing antibodies and cellular immunity. The conclusion states that developing an HIV vaccine remains a significant scientific challenge.

2. Dr. M. R. Kumbhare
Professor and HOD of
Pharmaceutical Chemistry
SMBT College of Pharmacy
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3.  Introduction
 Transmission of HIV
 Disease burden
 Historical perspectives on HIV vaccine development
 Structure of virus
 Challenges and difficulties in HIV vaccine development
 Immune response and antibodies
 Vaccine
 Conclusion
 Reference
Contents:-
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4. Introduction
 Vaccine:-
A vaccine is a substance stimulates an immune response that can either
prevent an infection or create a resistance to an infection.
 Human Immunodeficiency Virus (HIV):-
Human Immunodeficiency Virus (HIV) is a deadly and incurable illness
impacting millions annually. Targeting the T-helper CD4+ cells of the immune
system, HIV is a complex enveloped pseudo-diploid RNA virus. Of the nineteen
proteins encoded, one of the most readily produced and unique is the p24 inner
capsid protein.
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5.  The development of an HIV vaccine is a crucial component required to bring
the HIV epidemic to an end.
 Vaccine can be either therapeutic or prophylactic.
 Therapeutic Vaccine:-
Therapeutic vaccines are designed to control/clear HIV from already
infected individuals.
 Prophylactic Vaccine:-
Prophylactic vaccine are designed to reduce the risk of infection in people
who are not infected with HIV and also to reduce the viral load set point in people
infected with HIV.
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6. Transmission of HIV
 HIV transmission happens basically through homo-sexual or hetero-sexual intercourse, injection of
blood or blood derived products, and from mother to child throughout pregnancy, at delivery or
through breast feeding.
 It has been suggested that up to 50% of recent HIV infections are obtained from recently infected
individuals, due to both the high level of plasma microbial load throughout the first phase of disease
and to virus specific properties.
 Exit, Sufficient, Survive and Entry (ESSE) which are four necessary
conditions for HIV to be transmitted from a person living with HIV to
another person who are uninfected
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7. Disease Burden
 World Population: 783 million
 People living with HIV/AIDS (PLHA): 38.4 million
 Sub-Saharan Africa remained the most heavily affected
by HIV, accounting for 68% of all people living with
HIV and for 76% of AIDS deaths
 2.7 million new infection every year.
 India Population: 139.3 million
 People living with HIV/AIDS: 2.4 million.
 Annual New Infection are estimated at 62.97 thousand in
2021 in India.
 India is 3rd in absolute number of HIV cases.
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8. Historical perspectives on HIV vaccine development
 Three main approaches have dominated the development of an HIV
vaccine between 1987 and 2021.
 Each of these approaches involved one or more clinical trials.
 Although the first two approaches have largely been completed, it is
important to note that each approach has been continually re-examined
as researchers learn more.
1. In the late 1980s, the first approach focused on generating vaccine that
would induce neutralizing antibodies.
2. The second approach depended on giving a viral vector to a patient in
order to activate CD8+ T cells.
3. The third and most recent approach involves the use of 3 a heterologous
prime-boost to promote humoral and cell-mediated immune responses.
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9. Structure and Replication of virus
 Human Immunodeficiency Virus, the etiological agent of Acquired Immuno Deficiency Syndrome
(AIDS) belongs to the lentivirus subgroup of the family Retroviridae.
 HIV is a spherical enveloped virus about 90 to 120 nm in size.
 The nucleocapsid has an outer icosahedral shell and an inner cone-shaped core, enclosing the
ribonucleoproteins.
Figure: HIV virion structure
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10. Figure: Life cycle of HIV virus
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11. Challenges involved in the development
of HIV vaccine
 Over the years the major challenge in developing an effective HIV vaccine has
been the high rate of mutation and recombination during viral replication.
 High level of difficulty in generating a vaccine that can activate CD4+ T cells.
 Lack of a human model showing complete recovery from HIV infection and an
appropriate animal model to predict the potency of an HIV vaccine. This makes it
difficult to identify and induce immune response required to cure HIV infection.
 Lack of structural details of immunogens/antigens.
 Person to person variability in T-cell and antibody response induced by the
vaccine candidates.
 Designing an antigen binding to the B-Cell Receptor (BCR) with high affinity.
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13. Immune response and Antibodies
 Broadly neutralizing antibodies
 Broadly neutralizing antibodies are able to neutralize a wide variety of HIV strains
 Broadly neutralizing antibodies target specific vulnerable sites on the HIV
envelope, mediate neutralization and target infected cells for elimination.
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 Cellular immunity
 Measuring HIV specific T-cell immunity in a accurate way.
 Cellular immune response to the HIV, mediated by T lymphocytes, seems
string but fails to control the infection completely.
 Cell-mediated immunity-related protective factors have been clarified as a
result of efforts to understand the possibly protective immunological
response of people who are still resistant to HIV-1 infection

14. Vaccine
Vaccine
Live attenuated
vaccine
Inactivated
vaccine
Subunit
vaccine
Virus like
particles
DNA
vaccine
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15.  For the last two decades or so conventional vaccination methodologies have so far been
unsuccessful in eliciting strong immune responses against HIV and hence the field of HIV
vaccine research has focused on many alternative vaccine strategies.
 It is imperative to note that a successful vaccine needs to elicit both B cell and T cell
responses in order to be an effective preventive vaccine.
 At the beginning of this century, the rational creation and development of an HIV vaccine
that is safe, effective, and affordable remains to be a formidable scientific and public health
problem.
Conclusion
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16. References
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Infect Dis [Internet]. 2010;10(5):305–16. Available at: http://dx.doi.org/10.1016/S1473-
3099(10)70069-4
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17. 5) Gray GE, Laher F, Lazarus E, Ensoli B, Corey L. Approaches to preventative and
therapeutic HIV vaccines. Curr Opin Virol [Internet]. 2016;17(li):104–9. Available at:
http://dx.doi.org/10.1016/j.coviro.2016.02.010
6) Sauter D, Unterweger D, Vogl M, Usmani SM, Heigele A, Kluge SF, et al. Human
Tetherin Exerts Strong Selection Pressure on the HIV-1 Group N Vpu Protein.
2012;8(12)
7) Haynes BF, Moody MA, Alam M, Bonsignori M, Verkoczy L, Ferrari G, et al. Progress
in HIV-1 vaccine development. J Allergy Clin Immunol [Internet]. 2014;134(1):3–10.
Available at: http://dx.doi.org/10.1016/j.jaci.2014.04.025
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18. THANK YOU
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