• Caroline Forkin

The approval of the messenger RNA (mRNA) COVID vaccines marked the first time mRNA vaccines have been authorised for use outside of clinical trials, offering hope at the possibility of applying this technology to other infectious diseases, such as AIDS/HIV.

Despite the efficacy of pre-exposure prophylaxis (PrEP), ending the HIV epidemic requires a preventive HIV vaccine that can reach populations at risk where PrEP may not be approved, affordable and easily accessible. In addition, a vaccine could potentially help those struggling with adherence to daily oral medications or scheduling regular injections. According to one prediction, the added benefit of an HIV vaccine could mean that incident cases globally from 2015 to 2035 could decline by as much as 49 million.1

Yet, the development of a safe and effective HIV vaccine has been fraught with challenges and failures. The highly variable nature of the virus — along with its ability to target and impair important host immune cells, to integrate into the host genome early in infection, and to then establish latency — has increased the complexity of creating vaccines. Further, as there is no known natural protective immunity in humans, there are no immune correlates to guide vaccine development. Moreover, traditional vaccine strategies, such as non-live, freeze-dried vaccines and live attenuated vaccines, often underperform against some chronic or recurrent pathogenic infections, such as AIDS.2

However, advances in scientific knowledge and innovation — such as the new COVID-19 vaccines — can help to frame the research agenda around HIV vaccine research.

A brief history of mRNA vaccines in infectious disease

mRNA vaccines have long held huge promise in the eyes of the research community, having been studied in several infectious diseases such as influenza, Zika, rabies and cytomegalovirus.2 But, until recently, the development of mRNA vaccines ran into roadblocks, including its unstable nature and the fact that it is prone to degradation.2

The synthetic mRNA, a variation on the naturally occurring genetic material, directs the production of proteins in cells throughout the body in these vaccines. The benefit of this vaccine strategy includes its lack of infectious risk and ability to modify immune response through different formulations.3 In addition, these vaccines can be developed in a laboratory using readily available materials, leading to an easier manufacturing process that can be standardised and scaled up, creating a faster vaccine development than traditional methods of vaccine making.

Since mRNA vaccines had been studied before, scientists already had the basic tools to design the mRNA instructions for cells to build the unique spike protein into an mRNA vaccine as soon as the necessary information about the virus that causes COVID-19 became available. With perseverance and innovation from the scientific and clinical research communities, mRNA vaccines have finally achieved approval and are currently being distributed worldwide.

Potential for HIV mRNA vaccine

In Phase III studies, the COVID-19 mRNA vaccines have demonstrated promising results against SARS-CoV-2, especially in their ability to promote the production of neutralizing antibodies and T-cell responses.4,5 Using similar technology to the COVID-19 mRNA vaccine, a new investigational HIV vaccine from Moderna administers mRNA,6 “injecting” instructions for making viral proteins to stimulate an immune response in rhesus macaque monkeys. Specifically, scientists tested a vaccine that administers the genetic code for making envelope proteins from three clades, or types of HIV, as well as Gag proteins from the simian immunodeficiency virus, a strain of HIV that infects monkeys.

Another preclinical study found that immunisation of humanized mice with low doses of  a modified mRNA encoding monoclonal antibodies yielded high levels of protective antibodies against HIV-1 infection.7 Later, this same group found that a single immunisation with a low dose of the mRNA vaccine produced a strong T-cell response in mice and rhesus macaques.8 As T-cell responses are considered critical for eliciting antigen-specific, durable B-cell responses, this vaccine strategy is considered particularly promising.8

Another mRNA-based vaccine strategy that has produced promising immune responses in animal models is self-amplifying mRNA encoding glycoproteins.9 One research team demonstrated that this method could induce potent and durable T-cell responses in those mice who had been primed with the self-amplifying mRNA vector and boosted with a viral vector.9

Revolutionising vaccine research

The COVID-19 pandemic validated new ways of making vaccines, including using mRNA, revolutionising vaccine research and development. The speed to which COVID-19 vaccines are being developed is due to decades of research on other respiratory viruses and various preclinical mRNA vaccines. According to experts, the approach matured at the right time, noting that as of five years ago, the RNA technology would not have been ready.10

The success of the coronavirus vaccines not only provides hope for a HIV vaccine, but also may pave a pathway for other vaccines for infectious diseases such as tuberculosis and Zika. Moreover, mRNA vaccine technology is proving versatile, and has demonstrated preliminary efficacy in preclinical models for autoimmune diseases and cancer.2, 11  While the field of mRNA vaccines is still in its infancy, its potential to be a preferred vaccine strategy is promising.

 

Read more about HIV clinical research and ICON’s infectious disease experience.

Infectious diseases and vaccines insights

ICON's Infectious Diseases and Vaccines teams contribute regularly to media and industry conversations in addition to the production of thought leadership content in the form of whitepapers and blogs.

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References:

  1. Medlock J, Pandey A, Parpia AS, et al. Effectiveness of UNAIDS targets and HIV vaccination across 127 countries. Proc Natl Acad Sci U S A. 2017;114(15):4017–4022.

  2. Xu S, Yang K, Li R, Zhang L. mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection. International Journal of Molecular Sciences. 2020; 21(18):6582.       

  3. Jones LD, Moody MA, Thompson, AB. Innovations in HIV-1 Vaccine Design. Clinical Therapeutics. 2020 Mar; 42(3): 499–514. doi: 10.1016/j.clinthera.2020.01.009

  4. Polack, FP, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine 2020; 383:2603-2615. doi: 10.1056/NEJMoa2034577 

  5. FDA Briefing Document Moderna COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting December 17, 2020.

  6. Lusso P et al. Induction of cross-neutralizing antibodies and protection from heterologous tier-2 SHIV challenge by an mRNA-based vaccine in macaques. 23rd International AIDS Conference (AIDS 2020: Virtual), abstract OAALB0101, 2020 

  7. Pardi N, Secreto AJ, Shan X, et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat Commun. 2017;8:14630. doi:10.1038/ncomms14630

  8. Pardi N., Hogan M.J., Naradikian M.S. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018;215:1571–1588

  9. Bogers W.M., Oostermeijer H., Mooij P. Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion. J Infect Dis. 2015;211:947–955.

  10. Ball, Philip. The lightning-fast quest for COVID vaccines — and what it means for other diseases. Nature 589, 16-18 (2021)ndoi

  11. Garde, Damian. With success in vaccines, scientists try to turn mRNA against autoimmune diseases. STAT. 2021.