It is important that there are global networks of excellence that can rapidly facilitate basic and translational research in response to new and emerging pathogens. The recent Covid-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has highlighted the need for a collaborative response with different groups working together and sharing advances in ‘real time’.

Countries in continental Africa feel a disproportionate effect of emerging and endemic infectious diseases. It is of vital importance that centers of excellence, in academic and scientific research, are developed in Africa, and the regional transfer of technology and knowledge supported. It is imperative to support and equip investigators, institutions, and associated stakeholders in the countries most affected by the diseases to allow them a leading role and active participation in research programs.

Over the last two decades there has been sustained, and increasing, investment in the development of basic and clinical research capacity in Africa. ¹ There is need to encourage more inter-institutional South-South technology transfer, within Africa, during collaborative clinical research. This type of support allows local scientists to initiate and drive cutting-edge research in sub-Saharan Africa (SSA).

The majority of South-South Collaborations (SSC) for technology transfer are large and intergovernmental, mainly involving Latin American nations, SSA, India, and China; with countries from SSA largely being recipients. ² In the health sector, most SSC within SSA have been supported by international charities or have occurred during emergency situations, as seen during the Ebola disease outbreak in 2014-2015. ³ Mutual respect and benefit to all stakeholders is vital in all forms of the collaboration. Although there have been great achievements made through North-South collaborations, these may be accompanied with power imbalances. ^{2 , 4} There exists ample capacity and underutilized talent and expertise in Africa that must be harnessed to foster SSC, and efforts towards this are underway, for example through the African Network for Drugs and Diagnostics Innovation (ANDI), ⁵ the European and Developing Countries Clinical Trials Partnership (EDCTP)-supported networks of excellence (NoEs), ⁶ the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), ¹ and the International AIDS Vaccine Initiative (IAVI) network of independent partner research centers in SSA. ⁷

IAVI, with support from the United States Agency for International Development (USAID) and other international partners, have over the last 20 years developed a network of independent partner research centers in SSA and India to facilitate the design and testing of vaccines against HIV-1. This ‘network’ of independent groups has leveraged this capacity to perform research and clinical trials into a number of other endemic diseases within the region, such as tuberculosis and Ebola, as well as catalyzing roll-out of HIV treatment and prevention for at-risk groups. ⁸

Since the discovery of HIV-1, there has been a concerted effort to develop therapeutic and/or preventative interventions against the virus, including the development of an efficacious vaccine. While there have been a number of different approaches utilized in the design of vaccines, both in their composition and the vaccine regimen, the primary focus was initially based on assessing immune responses in peripheral blood to ‘triage’ vaccine candidates and determine potential vaccine efficacy in early phase studies. The vast majority of the global HIV-1 transmission occurs at the genital mucosa (cervico-vaginally, rectally, or through the penis foreskin, glans or urethra) during sexual intercourse. ⁹ It is in these mucosal compartments where the initial infection gains an early foothold and where a preventative vaccine or microbicide is likely to be required to act. We demonstrated a strict genetic bottleneck in the number of viruses that are transmitted and establish infection. ¹⁰ After several days, to weeks, the infecting virus replicates to such an extent that it passes through the draining lymph nodes ¹¹ into the peripheral circulation and other distal mucosal compartments, establishing infection and where it is likely to form a reservoir.

Many HIV vaccine and microbicide clinical trials are multisite and based in Africa and other low-middle income and resource-limited countries; which bear the burden of the HIV-1 pandemic and where HIV therapy, vaccines or other preventative interventions are most needed. In addition to the traditional approach of assessing systemic immune responses and depending on the vaccine mode of action, investigating the participant’s mucosal immune responses in clinical trials may be essential. Over the past few years, an increasing number of studies in SSA outside of South Africa have included mucosal sampling in such trials. Past studies have demonstrated the presence of HIV-relevant immune responses at mucosal sites. ¹² Moreover, the field of vaginal microbiome (VMB) has lately attracted significant interest due to the role of VMB in the transmission of genital infections, including HIV. Although VMB studies have been scarce in Africa, this in now changing especially with the recognized role of VMB in the transmission of HIV. ^{13 – 16}

Feasibility studies from Kenya showed that study participants accepted several mucosal sampling techniques from the genital and non-genital mucosal sites. ^{12 , 17} For comparable data across studies and research centers, mucosal samples should be obtained in a standardized and reproducible manner. Unlike blood sampling, mucosal sampling methods have not been widely standardized, with many groups using different sampling equipment and methods, compromising data comparability and reproducibility across studies and study centers.

To foster inter-institutional South-South technology transfer, Kenya AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR) developed a mucosal training program to help standardize sampling and processing methods across the region and address the capacity gap in mucosal sampling techniques and immunology in Eastern Africa. While this was focused on developing and testing HIV-1 vaccines, the approaches developed can be used in a range of fields and diseases.

Development of the mucosal procedures: Clinical and laboratory SOPs were developed for the collection, processing and storage of: -

Rectal and cervical secretions using Merocel sponge;

These methodologies were subsequently successfully applied in three epidemiological mucosal studies at KAVI-ICR in the years 2009 to 2013 and thereafter in four collaborative Phase 1 HIV vaccine clinical trials, a Varicella Zoster vaccine trial, basic science studies, and most recently an HIV broadly neutralizing antibodies clinical trial. ( Table 1)

Mucosal training: We, since the year 2011, have trained eight research centers from Uganda, Rwanda, South Africa and Kenya. The centers were KEMRI/WRP-Kericho Kenya, CFHR Kigali Rwanda, KEMRI-CGMRC Kilifi Kenya, MRC/UVRI & LSHTM Uganda, WRHI South Africa, PHRD Kiambu Kenya, and IDI Kasangati Uganda. All the centers, except WRHI, received training on the sampling of cervicovaginal mucosal secretions using the merocel sponge and/or Instead Softcup, while one center did not receive training on sampling of rectal secretions. Additionally, CFHR Rwanda received training on the collection of oral and upper respiratory secretions; KEMRI/WRP-Kericho and KEMRI-CGMRC Kilifi received training on rectal and cervical cell sampling using the cytobrush; KEMRI-CGMRC Kilifi further received training on rectal biopsy sampling using pinch forceps. CFHR, IDI, WRHI, PHRD, and UVRI-IAVI received training on rectal sampling using the OriCol rectal device in the year 2021. CFHR, MRC/UVRI & LSHTM, UVRI-IAVI, KEMRI/WRP, KEMRI-CGMRC, and PHRD had physical training; all three centers from Kenya received training at KAVI-ICR, while three centers from outside Kenya received training on-site at the trainees’ research centers. In the year 2021 all (four) centers from outside Kenya (CHFR, UVRI-IAVI, IDI, and WRHI) received training online. ( Table 2)

A total of 108 research staffs received training with CFHR having the highest number of trainees (n=34, 32%). The trainees’ cadres included physicians/clinicians (28%), nurses (33%) and laboratory technologists (39%). ( Figure 2)

All the centers that received training have since applied the skills learnt into a range of mucosal immunological studies. CFHR, Rwanda applied the mucosal skills in a collaborative multi-country observational study (with St. Mary’s Hospital, London, UK and KAVI-ICR), ¹² and during a clinical trial in collaboration with KAVI-ICR, Kenya, and St. Stephens AIDS Trust, London, UK ^{12 , 17 , 23} ; the resulting mucosal immunological assay results were comparable across the participating sites. CFHR Rwanda, IDI Uganda, PHRD Kenya, UVRI-IAVI Uganda, WRHI South Africa, and KAVI-ICR Kenya are all applying the mucosal techniques in an ongoing multisite clinical trial; in this clinical trial KAVI-ICR is the regional center for the mucosal assays. ²⁵

Furthermore, laboratory personnel from three research centers in India were also trained in the laboratory methods developed by KAVI-ICR. These included staff at the National AIDS Research Institute Pune, YRG Care Chennai, and National Institute for Research in TB, Chennai; the training provided included mucosal samples processing, storage and immunological assays.

We present a paper describing how a center of excellence at KAVI-ICR, Nairobi, Kenya, supported by IAVI, USAID and multiple international donors has developed inter-institutional South-South collaborations in Africa through facilitating technology transfer and the sharing of experiences and best practices in mucosal immunological studies. KAVI-ICR spearheaded successful mucosal studies and the transfer of technology to other SSA research centers, making it possible to standardize mucosal sampling and processing across the research centers, obtaining analogous samples that yield comparable data. ^{12 , 23}

The development of mucosal studies led to an increase in basic research, and resulted in the development of clinical trials in which assessment of mucosal responses is embedded within the clinical trial protocol. ^{17 , 23 , 25 , 26} Consequently, in collaboration with IAVI’s USAID-funded mucosal immunology program, the IAVI extended network of clinical research centers developed a ‘blanket’ protocol to allow the collection of peripheral and limited mucosal samples in order to support the transfer of knowledge and training in these standardized methods, and to allow rapid sample collection for collaborative pilot studies to generate preliminary data. ²⁷ While focused on studies that support the development of an HIV-1 vaccine, these methods are available to new collaborators to kick-start collaborative studies and utilize the capacity developed in these state-of-the-art clinical research centers. Indeed, these methods have already been applied in a varicella zoster vaccine study at KAVI-ICR in collaboration with University of Toronto. ²⁶

Importantly the nature of mucosal immunology and its requirement for fresh assays to be performed on site has facilitated the engagement of local staff at the research centers and the development of increased staff and infrastructure capacity on site. This has allowed local scientists to drive aspects of research to develop their own careers, actively engage with the project teams, and develop lasting collaborations and mentorship with international partners.

For example, researchers at KAVI-ICR are now employing the Widefield microscopy technology to studies assessing the replication of HIV transmitted/founder viruses in cervical and rectal tissues ex vivo, mucus mobility studies, and human tissues studies for HIV reservoirs. ²⁸

Although our program was initially designed for in-person delivery we were, out of necessity, able to successfully execute an online training as well. The four sites that were trained online have subsequently successfully applied the mucosal techniques in a multisite and multi-country clinical trial, ²⁵ from which we anticipate a yield of comparable data. One of the advantages of online training is the savings on travel and accommodation costs; such savings should be desirable especially in the SSA region where resources are limited. Therefore, online options for SSC in capacity building need to be purposely promoted. ²⁹ For this the SSA institutions can seek support from organizations such as the South-South Galaxy which fosters online SSC through advisory services, capacity advancement, linkage to experts, among others. ³⁰

Another addition to our original design of the program was the extension of the technology transfer program outside the African continent, supporting training of partners in India. We have thus been able to progress from purely transferring methods in a North-South manner to supporting North-South-South-North collaborations for technology transfer.

We successfully established and implemented a South-South mucosal training program in SSA. Our venture for sharing of experiences and best practices, also yielded collaborative research projects across the participating sites. This initiative has now expanded into a state-of-the-art mucosal immunology program, through which KAVI-ICR has expanded its research portfolio.

Lessons from our mucosal capacity building program can be extrapolated to SSC for capacity strengthening and technology transfer in other areas of the clinical research processes spectrum - from research conceptualization, grant writing, research inception and conduct, up to dissemination of research findings.

SSC in research should be encouraged; through this, robust local networks of excellence for expanded collaborative research are realizable. Additionally, pulling together in the principle of horizontality is beneficial for balanced and triangular cooperation in research. Through such initiatives, supported by international donors, the development of regional capacity and expertise is possible. The established expertise can be leveraged when needed, and also builds the capability for African scientists to engage at an international level, actively participating in driving internationally relevant research.