A recent Immunological Reviews study highlights how global virology and immunology networks that were originally developed for human immunodeficiency virus (HIV) vaccine research were rapidly adapted to study the pathogenesis of the coronavirus disease 2019 (COVID-19).

Study: Leveraging South African HIV research to define SARS-CoV-2 immunity triggered by sequential variants of concern. Image Credit: MIND AND I / Shutterstock.com

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing COVID-19 pandemic, has changed the paradigm of how we understand immune responses. In particular, COVID-19 research has elucidated the role of B-cells in the adaptive humoral immune system and the impact of vaccination on respiratory viruses.

Furthermore, the rise of population immunity acquired from targeted responses against highly immunogenic regions of SARS-CoV-2 has been a strong driving force in the emergence of progressively mutated SARS-CoV-2 variants throughout the COVID-19 pandemic.

Most countries in the world contributed to SARS-CoV-2 research. For example, several important contributions came from South Africa, where the epidemic has been characterized by four epidemiological waves between March 2020 and February 2022.

The current study describes how South African HIV research can be leveraged to define SARS-CoV-2 immunity triggered by sequential variants of concern.

The breadth of HIV research in South Africa

In South Africa, researchers studying HIV have built up their next-generation sequencing expertise and infrastructure primarily through routine HIV antiretroviral drug resistance surveillance, as well as through basic virological studies on HIV to inform vaccine design. In fact, many South African laboratories have been profoundly involved in HIV vaccine and treatment research since the 1990s. This commitment to HIV research is largely due to significant global investments in South African laboratories and clinical trial infrastructure.

Antibody research, combined with the need for result comparison among laboratories, resulted in the development and utilization of standardized pseudovirus neutralization assays with the use of engineered cell lines to decrease the level of variability. Consequently, many research groups acquired significant experience in pseudovirus neutralization assays and single B-cell isolation methods, as well as in technologies to study T-cells in HIV infection. 

A direct value for the COVID-19 pandemic

Such vast experience quickly enabled South African researchers to merge real-time genomic surveillance to immunological platforms in order to characterize immune responses elicited by infection with specific SARS-CoV-2 variants in sequential epidemic waves. The study of vaccination and hybrid immunity, the latter of which is defined as the combination of infection- and vaccination-induced immunity, was also possible.

It is very unlikely that researchers will be able to instigate high neutralizing antibody titers in the respiratory mucosa for protracted time periods, thus limiting the ability to completely prevent SARS-CoV-2 infection from occurring. Nevertheless, the presence of antibodies may be sufficient to dampen the viral load and influence disease outcomes.

This response is evident in individuals with breakthrough infections who often exhibit lower viral loads. Such immune responses reflect the rapid recall of memory B-cell responses, as well as their efficacy in reducing the spread of SARS-CoV-2 and its variants, both within the infected individual and to other people.

Despite the prevailing public opinion in South Africa and elsewhere implying that this pandemic is over, many studies have demonstrated why it remains pivotal to extend vaccine coverage in Africa and other low- and middle-income countries, even if only single-dose vaccine regimens are feasible.

The need for continuous genomic surveillance

By using the example of South Africa, it appears likely that the waning of antibody responses represents a significant contributing factor to the timing of outbreak resurgence and, in turn, the selection of novel viral variants.

Despite the fact that the current globally dominant variant, Omicron, appears to have decreased disease severity compared to previous variants of concern, it is highly likely that we will continue to see the selection of new variants periodically.”

This is likely to occur, given what we know about SARS-CoV-2 evolution due to selection pressure induced by population immunity, which will increasingly become more hybrid-like and therefore more diverse.”

Thus, genomic surveillance for SARS-CoV-2 must continue through established sentinel surveillance systems like the Global Influenza Surveillance and Response System (GISRS) through influenza-like illness and severe acute respiratory illness detections and characterization. Such immunology insights will pave the way to optimal pandemic responses in the future.

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.