Adopting an heterologous prime-boost strategy in COVID-19 vaccination: the need for locally generated evidence in Africa

¹Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia, ²Malaria Genomic Epidemiology Network, Nigeria, Nigerian Institute of Medical Research, Lagos, Nigeria, ³Field Presence, World Health Organization, Adamawa State Field Office, Adamawa, Nigeria, ⁴Research and Development Blueprint Unit, World Health Organization, Geneva, Switzerland

^&Corresponding author
Mary Aigbiremo Oboh, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia

Commentary    

The detection of the novel coronavirus disease (COVID-19) in China; in December 2019 and its subsequent declaration as a public health emergency of international concern on 30 January 2020 has significantly impacted global health systems, economies, and travel. The African region has recorded a relatively modest infection rate of infection. As of 2 September 2021, Africa has an estimated 7 849 859 cases and 198 132 mortality, representing 0.04% and 0.04% of the global estimates [1]. In the absence of effective treatment, the rapid development of vaccines using innovative platforms offers a glimmer of hope. The World Health Organisation (WHO) has approved some of the vaccines for emergency use [2]. With the tremendous success of COVID-19 vaccine development, it becomes imperative to set a robust strategic plan for equitable distribution, affordability, and accessibility to every individual regardless of political, racial or cultural background.

Consequently, WHO, in partnership with the Coalition for Epidemic Preparedness Innovation (CEPI), GAVI, the Vaccine Alliance, set up the COVID-19 Vaccines Global Access (COVAX) Initiative, which aims to accelerate the manufacture and equitable access of COVID-19 vaccines to all countries irrespective of their economic status. The COVAX initiative proposed to deliver approximately 2 billion doses of COVID-19 vaccines by the end of 2021 to frontline workers and individuals who are >65 years with or without co-morbidities. At conception, the ultimate goal of this distribution initiative is to prevent discrimination between high and low income/middle income countries (LMICs), and in turn, ensure equitable vaccine distribution. COVAX and the World Bank hopes to accelerate COVID-19 vaccine supply for developing countries through a new financing mechanism that builds on GAVI´s newly designed arthrogryposis multiplex congenita (AMC) cost-sharing arrangement. Therefore, countries within the African region can capitalise on this distribution plan to access the COVID-19 vaccine and effect strategic distribution across the continent and nationwide. However, hoarding and vaccine nationalism by wealthier nations have slowed the COVAX initiatives' implementation and hindered the realization of its ambitious drive. The first COVID-19 vaccine sent to most countries in the region through the COVAX initiative was the Oxford AstraZeneca (ChAdOx1 nCoV-19) vaccine. However, the supply dwindled due to a decline in production capacity caused by an upsurge in COVID-19 cases in India, where the manufacturer (Serum Institute of India, Pvt) of AstraZeneca vaccine is located.

As of 9^th August 2021, reports on COVID-19 vaccination coverage have not been encouraging in countries within the African region. Only 1.56% and 3.71% of the population have received two (2) and one (1) doses of the various COVID-19 vaccines. Only two countries have vaccinated more than 50% of its population (Seychelles- 95% and Mauritius - 75%), and six have vaccinated almost a quarter of its population (Morocco, South Africa, Djibouti, Equatorial Guinea, Eswatini, and Cape Verde), while some (Burundi, Eritrea and Sierra Leone) are yet to provide any vaccination indices [2]. The setbacks in access and coverage would impact on transmission negatively and spread of variants SARS-CoV-2 strains by each country and the continent in general, given the suboptimal adherence to public health and social measures.

As a result of the changing recommendations on the use of the Astrazeneca vaccine regarding its reduced protection against variants of concern in some countries [3], high income countries are now recommending that individuals previously primed with the Astrazeneca vaccine should receive an alternative vaccine as their second (boost) dose. In addition, alternative prime-boost vaccination has been found to provoke superior immunogenicity and enhanced protection against SARS-CoV-2 [4] as well as against Ebola [5]. mRNA vaccine has been suggested as a reliable boost dose [6]. Hence, a heterologous prime-boost COVID-19 vaccine scenario is gaining prominence. Consequently, with African countries getting various COVID-19 vaccines based on different technology platforms, secured through different initiatives, to ensure as much coverage as possible, (Table 1, Table 1 (suite), Table 1 (suite 1), Table 1 (suite 2)) it is expected and indeed planned by some of these countries that most people who received an incomplete Astrazeneca dose (a single dose of the vaccine), or have not received any vaccination, will receive a second (for complete vaccination) or full dose course of another vaccine. Theoretically, this serves as the booster vaccine.

Although, some studies which evaluated heterologous prime-boost COVID-19 vaccine of different platforms have reported higher frequency of spike-specific CD4+, CD8+ T-cells [4], strong and high titers of neutralising antibodies against B1.1.7 and B.1.351 strains [6,7]. Reactogenicity after heterologous boost was reported as vaccine unrelated in one study (flu-like illness, headache, asthenia) [8], while another [9] attributed increased systemic reactogenicity after boost dose to heterologous manner. The Shaw [9] study which was conducted in individuals >50 years and older in the UK, suggested that reactogenicity might be higher if younger individuals were administered heterologous prime-boost doses. Although the reactogenicity observed is short-term, such trial needs to be replicated in various populations with the different vaccine combinations intended for implementation. All the aforementioned studies were conducted in Germany, Russia, China, and the UK. None has been conducted in any African countries that have or are about to commence implementing heterologous boost dose. A thorough search of clinical trial registries (clinicaltrial.gov, ICTRP, ISRCTN, PACTR, etc.) for COVID-19 heterologous vaccine efficacy regrettably did not return any hit from any African country. The importance of carrying out such a study in different African settings/countries cannot be overemphasised, especially as the emergence of new variants is quite rapid.

Conclusion     

Globally, heterologous prime-boost vaccines offer enhanced protection in comparison to homologous vaccine, however, it is important that prior adoption, safety and reactogenicity data be locally generated in populations where such heterologous vaccine is to be implemented. Therefore, this treatise advocates an experimental arm to generate robust evidence on immunogenicity, reactogenicity and safety of heterologous prime-booster within the African population, even in countries that have commenced the roll-out. This will provide an empirical evidence to guide this innovative approach aimed at ensuring equity and access to COVID-19 vaccines in LMICs, particularly countries within the African region.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All the authors have read and agreed to the final manuscript.

Tables     

Table 1: different COVID-19 in African countries and percentage of population vaccinated

Table 1 (suite): different COVID-19 in African countries and percentage of population vaccinated

Table 1 (suite 1): different COVID-19 in African countries and percentage of population vaccinated

Table 1 (suite 2): different COVID-19 in African countries and percentage of population vaccinated

References