Recent Progress Toward an HIV-1 Vaccine

Since it was first reported in 1981, The human immunodeficiency virus (HIV) has been a major cause of morbidity and mortality across the world. Today, more than 38 million people are living with the virus.¹ Although there are now antiretroviral therapies which can suppress viral replication—and which have significantly improved patient life span and quality—there is a constant threat of drug resistance and side effects of long-term medications. Critically, these treatments cannot fully prevent or cure HIV infection, although they can be used for pre-exposure prophylaxis in people at high risk.

An HIV vaccine is urgently needed but has been difficult to develop, due in part to HIV’s high level of genetic variation. Because the virus quickly accumulates mutations, there may be several HIV variants circulating at the same time within a single individual.² The core danger of HIV is that it infects the immune cells that are normally involved in fighting off viral infections. To address this, researchers have looked at both neutralizing and non-neutralizing antibodies, as well as T-cell mediated responses.³ Despite this, HIV vaccine trials have failed, with only one showing even modest efficacy—but there may be other promising approaches on the horizon.

Some innovative nanomaterials have been shown to both increase storage potential and enhance the immune response to protein antigens. Nanovaccines are generally 1–100 nm and can include biological macromolecules, polymers, metals, etc.—but all can carry and present antigens in native-like conformations, and they have also been shown to increase immunogenicity. Now, researchers are exploring these nano options in the fight to develop potent and effective ways to prevent against HIV infection.

A research team in China recently designed a new HIV-1 envelope glycoprotein nanoparticle (Env/NP) vaccine using amphiphilic polymers.⁴ To evaluate immunogenicity, they immunized three groups of rabbits with Env/NP alone, an adjuvant alone, and both, respectively. After two weeks, blood samples indicated that the combination of Env/NP and adjuvant induced the highest immune responses. In addition, the Env/NP vaccine induced more potent and broader neutralizing activities against multiple HIV-1 subtypes. A bonus is that the vaccine is stable at room temperature, a key benefit compared to traditional protein-based vaccines which require cold chain storage and transport—a factor that can significantly drive up the cost of vaccination. The authors are optimistic that this novel approach may be applicable to other protein-based vaccines, helping to both enhance their ability to create an immune response and make them more resistant to higher temperatures.

Another recent approach looks at broadly neutralizing antibodies (bnAbs)against HIV-1 envelope glycoproteins.⁵ These target vulnerable sites that are critical for virus entry and tend to be conserved among different strains even when there is genetic variation. Although bnAbs occur only in low numbers in natural infection, it may be possible to deliver therapeutic levels that are effective against a range of HIV strains. With this in mind, the neutralizing epitopes defined by HIV-1 bnAbs are being used for vaccine design. More information is needed about cellular responses, but hopes are high that in the future it will be possible to reduce the transmission of this deadly virus.

Explore Related Research from ACS Journals

A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells
DOI: 10.1021/acschembio.2c00515

Indirect Mechanisms of HIV-1 Evasion from Broadly Neutralizing Antibodies In Vivo
DOI: 10.1021/acsinfecdis.2c00573

Large-Scale Synthesis of Man₉GlcNAc₂ High-Mannose Glycan and the Effect of the Glycan Core on Multivalent Recognition by HIV Antibody 2G12
DOI: 10.1021/acsinfecdis.2c00442

References

1. Global Statistics. HIV.gov 2022.
2. Satyanarayana, M. Another HIV vaccine fails, highlighting long-standing challenges in the field. Chemical & Engineering News 2021, 99, 34, 16–17.
3. Herschhorn, A. Indirect Mechanisms of HIV-1 Evasion from Broadly Neutralizing Antibodies In Vivo. ACS Infect. Dis. 2023, 9, 1, 5–8.
4. Xin, X. et al. Improvement of B Cell Responses by an HIV-1 Amphiphilic Polymer Nanovaccine. Nano Lett. 2023, 23, 9, 4090–4094.
5. Kumar, S. et al. An Overview of Human Anti-HIV-1 Neutralizing Antibodies against Diverse Epitopes of HIV-1. ACS Omega 2023, 8, 8, 7252–7261.