Russia’s Sputnik V COVID-19 vaccine is unlikely to be rolled out any time soon in this country, with the SA Health Products Regulatory Authority (SAHPRA) holding back on approval after research showing vaccinated men risk contracting HIV.
The vaccine was developed by the Gamaleya Research Institute of Epidemiology and Microbiology in the Russian Federation, and the locally licensed applicant is Lamar International.
In a statement issued this week, SAHPRA CEO Dr Boitumelo Semete-Makokotlela said they had been “engaged in a rolling review of the data for the Sputnik V vaccine since the application was first submitted in February”.
The Sputnik V vaccine combines two separate adenovirus-vectored constructs, one relying on the Adenovirus Type 26 (Ad26) and the other on Adenovirus Type 5 (Ad5), as the delivery vehicles for the antigen. Concerns have been raised about the safety of Ad5-vectored vaccines in populations at risk for HIV infection. One is the presence of pre-existing Ad-specific neutralising antibodies (NAbs) in the general population.
The safety of adenovirus vaccine vectors has been evaluated in various clinical trials: the STEP trial (which primarily recruited gay men in the Americas) and the PHAMBILI trial (heterosexual men and women in South Africa) were both considered. Both were designed to administer three doses of an Ad5-vectored vaccine encoding the HIV gag, pol and nef proteins.
SAPHRA says that in both trials, administration of an Ad5-vectored vaccine was associated with enhanced susceptibility/acquisition of HIV in men. The STEP trial was stopped in September 2007 due to lack of efficacy, but evidence quickly emerged of an enhanced risk of HIV infection in a particular subgroup of participants (uncircumcised men with high titers of pre-existing antibodies to Ad5).
Over extended follow-up, the increased risk of HIV among vaccine recipients became statistically significant when the entire trial population was analysed. The STEP trial results led to the early cessation of the PHAMBILI trial and while initial results from PHAMBILI did not show enhanced HIV risk, this risk was later confirmed after extended follow up.
SAPHRA said that during the assessment of the application for approval of the Sputnik V vaccine, it had reviewed the outcomes of the STEP and PHAMBILI trials in detail, as well as the arguments advanced in a commentary in Lancet in 2020, which pointed to confirmatory data from a non-human primate challenge study. SAPHRA had then asked for data demonstrating the safety of the Sputnik V vaccine in settings of high HIV prevalence and incidence, but “the applicant was not able to adequately address this request”.
To date, the Sputnik V COVID-19 vaccine has not received Emergency Use Listing by the World Health Organization, with the recent WHO update indicating that the process is “on hold, awaiting completion of rolling submission”.
SAHPRA has resolved that the application for Sputnik V should not be approved right now, and has expressed concern that use of the vaccine in South Africa, a setting of a high HIV prevalence and incidence, may increase the risk of vaccinated males acquiring HIV.
The review of Sputnik V will, however, remain open for submission of relevant safety data in support of the application.
Semete-Makokotlela added that there had been media reports that applications for approval of the Ad26-vectored component only (denoted as Sputnik Light) were expected to be submitted to numerous national medicines regulatory authorities, but SAHPRA has not yet received an application for this.
See more from MedicalBrief archives:
Sputnik vaccine’s backers attack SAHPRA over emergency authorisation
Sputnik V vaccine efficacy against SARS-CoV-2 variants — Small Argentina study
Argentina's president tests positive despite taking Sputnik V vaccine
EFF: SAHPRA refusal to allow Sinovac and Sputnik condemned