Cuba’s COVID Vaccine: Development, Safety, and Efficacy

Cuba developed two homegrown COVID-19 vaccines, Soberana 02 and Abdala, both built around a small but critical piece of the SARS-CoV-2 spike protein called the receptor-binding domain. In phase 3 clinical trials, each vaccine reached roughly 92% efficacy against symptomatic disease, and real-world data from Cuba’s mass vaccination campaign broadly confirmed those numbers. The vaccines rely on protein-based technology rather than mRNA, which gives them practical advantages in storage and distribution but also meant they arrived with less international fanfare than Pfizer or Moderna.

How the Two Vaccines Work

Soberana 02 is a conjugate vaccine, a design borrowed from the approach long used against bacterial diseases like meningitis and Haemophilus influenzae type b. The vaccine links a lab-made copy of the RBD to tetanus toxoid, a carrier protein that most people’s immune systems already recognize from childhood immunizations.¹ The idea is that the tetanus toxoid acts as an immune-system amplifier: it recruits T-helper cells, which strengthen the antibody response against the attached RBD and promote longer-lasting immune memory. Preclinical work showed that these RBD–tetanus toxoid constructs triggered strong neutralizing antibody responses in animals, with a heavy bias toward the mature, high-quality antibodies you want from a vaccine.² The standard schedule calls for two doses of Soberana 02 followed by a third dose of a related product called Soberana Plus, which contains a dimeric form of the RBD. That heterologous three-dose regimen is the one that produced the headline efficacy numbers.

Abdala takes a more conventional protein subunit approach. It uses the same RBD target but produces the protein in yeast cells (Pichia pastoris), a well-established manufacturing system in biotech.³ The vaccine is formulated with an aluminum hydroxide adjuvant and given in three intramuscular doses spaced two weeks apart. Abdala was developed by Cuba’s Center for Genetic Engineering and Biotechnology (CIGB), while the Soberana line came from the Finlay Vaccine Institute. Both institutions have decades of experience making and exporting vaccines, and their COVID programs drew on infrastructure that had been built up since the 1980s.

Phase 3 Efficacy in Adults

The Soberana phase 3 trial enrolled tens of thousands of adults in Havana and tested the heterologous three-dose schedule (two shots of Soberana 02 plus one of Soberana Plus) against placebo. In the final analysis, symptomatic COVID-19 was confirmed in 35 people in the placebo group versus 6 in the vaccine group, yielding an efficacy of 92.0% against symptomatic infection. All six cases of severe COVID-19 occurred in the placebo arm, and no one in either group died of the disease.⁴ The phase 2b trial that preceded it showed a seroconversion rate of about 76% after two doses, jumping to nearly 97% once the Soberana Plus booster was added. Neutralizing antibodies were detected against multiple variants of concern, and functional antibodies persisted seven to eight months after the third dose.⁵

Abdala’s phase 3 trial, also placebo-controlled and double-blind, produced strikingly similar numbers. Symptomatic COVID-19 was confirmed in 142 placebo recipients and only 11 in the vaccine group, for an efficacy of 92.28%. Against moderate and severe disease the efficacy was about 93%, and all five critical patients (four of whom died) were in the placebo arm.⁶ These trials were conducted during the Delta wave in Cuba, so the efficacy figures reflect performance against a variant that was causing serious illness worldwide at the time.

Safety Profile

Both vaccines showed reassuringly mild side-effect profiles in their trials, something that protein subunit vaccines are generally known for compared with other platforms. In the Soberana phase 3 trial, local reactions at the injection site (mostly pain) occurred somewhat more often in vaccine recipients than in placebo recipients after the first dose, at about 8% versus 3%, but the gap narrowed with subsequent doses and dropped below 1% after the third shot. Nearly all local reactions were graded as mild, and the median duration was about two days. Systemic side effects like headache or fatigue occurred in fewer than 2% of vaccine recipients after the first dose and dropped further with each subsequent injection. The rate of serious adverse events was essentially the same in the vaccine and placebo groups.⁴

Abdala’s safety data followed the same pattern. In a pediatric trial that also tested the vaccine in adults as a comparator group, about 38% of participants reported at least one adverse event, but most were mild injection-site pain that resolved within a day or two. Three children were hospitalized during the trial for what turned out to be dengue fever infections, events the investigators classified as coincidental and unrelated to vaccination. No clinically meaningful changes in laboratory values were tied to the vaccine.⁷ Neither vaccine has been linked to the rare inflammatory side effects that generated concern around some other COVID-19 platforms, such as myocarditis with mRNA vaccines or thrombosis with adenoviral-vector vaccines. That said, Cuba’s pharmacovigilance system is less resourced than those in wealthier countries, so very rare events might be harder to detect at population scale.

Real-World Effectiveness

Trial efficacy numbers tell you how a vaccine performs under controlled conditions. What matters more is how it holds up once millions of people are getting jabbed in clinics and pharmacies. A large cohort study in Havana tracked Abdala recipients during the Delta wave and found the vaccine was about 98% effective at preventing severe disease and about 99% effective at preventing death among fully vaccinated people. Even those who had only received a partial course were protected at rates above 93%.⁸ Those real-world numbers actually exceeded the trial efficacy, likely because the cohort study measured protection against the outcomes that matter most (hospitalization and death) rather than any symptomatic infection.

The Soberana vaccines were also tracked in the real world, including in pediatric populations during the Omicron wave. A study of children aged 2 to 11 who received the Soberana 02 plus Soberana Plus regimen found effectiveness against severe disease of 95% or higher, depending on the age group, and no child deaths from COVID-19 were observed. Protection held up over at least six months of follow-up.⁹ The fact that the Soberana data held up against Omicron, a variant that largely evaded the neutralizing antibodies generated by the original strain vaccines, is noteworthy. It suggests that the protein conjugate approach may have some cross-variant resilience, though how much protection would persist against later subvariants is an open question.

Vaccinating Children

Cuba was unusually early in extending COVID-19 vaccination to children, beginning pediatric rollouts before many wealthy countries had even authorized shots for that age group. Both vaccines were tested in children and adolescents through formal clinical trials.

The ISMAELILLO trial tested Abdala in children aged 3 to 18 across two dose strengths. Both were well tolerated, with injection-site pain as the most common complaint. Side effects decreased with each successive dose. No serious vaccine-related adverse events were recorded.⁷ A follow-up open-label phase 2 trial, MEÑIQUE, tested Abdala in over 700 children and adolescents and used a non-inferiority design comparing the antibody response in children to that in adults. Children aged 3 to 11 produced neutralizing antibody levels that were statistically non-inferior to adults, and adolescents showed a similar pattern. About 38% of participants experienced at least one adverse reaction, overwhelmingly mild and short-lived.¹⁰

For the Soberana line, pediatric data on immune durability showed that T-cell responses (measured by cells producing interferon-gamma in response to the RBD) held steady at six months post-vaccination compared to levels recorded two weeks after the third dose. This was true regardless of whether children had prior natural infection.¹¹ Durable T-cell immunity matters because antibody levels tend to wane over months, but cellular immunity provides a backstop that helps prevent severe disease even when circulating antibodies decline.

How Immune Protection Lasts

One of the questions that followed every COVID-19 vaccine was how long protection would last. For the Soberana regimen, the phase 2b trial detected functional antibodies seven to eight months after the third dose, suggesting that the conjugate design delivers a reasonably sustained antibody response.⁵ The researchers attributed part of this durability to the tetanus toxoid carrier protein, which recruits T-helper cells and promotes the kind of immune memory that outlasts the initial burst of antibodies.⁴ The pediatric durability data described above reinforces this picture: T-cell responses were stable at six months, which is a good sign for sustained protection against severe outcomes.

That said, durability data beyond about eight months remain limited in the published literature for both Cuban vaccines. Like every other COVID-19 vaccine, waning antibody levels over time are expected, and Cuba administered booster doses to its population. The RBD-focused design also means the vaccines are targeting a region of the spike protein that mutated significantly in later Omicron subvariants, which likely reduces neutralizing antibody efficacy against newer strains, even if T-cell immunity continues to help against severe disease.

Cold-Chain Advantages and Logistics

One of the most practical selling points of Cuba’s vaccines is how easy they are to store and ship. Both Soberana 02 and Abdala are stable at standard refrigerator temperatures of 2 to 8°C, the same cold-chain infrastructure used for routine childhood vaccines everywhere in the world.⁴ This contrasts sharply with the mRNA vaccines that dominated early pandemic supply: Pfizer’s vaccine initially required ultra-cold storage at minus 70°C, and Moderna’s needed minus 20°C, conditions that are nearly impossible to maintain across rural or tropical settings in lower-income countries.

For Cuba itself, where the existing healthcare infrastructure reaches remote communities through a network of family-doctor offices and neighborhood polyclinics, the cold-chain simplicity meant the vaccines could move quickly from factory to arm without requiring any new equipment. The country’s vaccination campaign ultimately reached the vast majority of its population, including children as young as two, and public-health officials credited the rapid, community-based rollout with helping drive a sharp decline in cases, severe disease, and deaths.⁸ The affordability and cold-chain friendliness also position protein subunit vaccines well for future pandemic preparedness in settings where ultra-cold storage will never be realistic.

Technology Transfer to Iran

Cuba has a long history of exporting vaccine technology, and the COVID-19 vaccines were no exception. The most documented example is the transfer of Soberana Plus production technology to Iran, where the vaccine was manufactured domestically under the trade name PastoCovac Plus. Iran received the technology at the formulation stage, meaning it could produce the final product locally once quality benchmarks were met.¹² A comparability study showed that the Iranian-made vaccine matched the Cuban original in terms of quality, safety, and immune response, providing some of the first published data on whether a protein subunit COVID vaccine could be reliably replicated by another country’s manufacturing system.

Several other countries, including Venezuela, Vietnam, and Nicaragua, either imported Cuban vaccines or explored local production agreements, though published comparability data from those partnerships are scarcer. The technology transfer model is significant because it represents an alternative to the COVAX-style donation approach: rather than shipping finished doses, Cuba offers production know-how that could leave the recipient country better prepared for the next outbreak. Whether this model scales depends heavily on the recipient country’s existing biotech capacity and regulatory environment.

Why These Vaccines Remained Relatively Unknown

Despite strong trial results, Cuba’s vaccines never achieved the global profile of Pfizer, Moderna, or even AstraZeneca. Several factors explain this. Cuba did not seek WHO Emergency Use Listing for Soberana or Abdala, partly because the regulatory process requires resources and data-sharing infrastructure that the country’s institutions found difficult to marshal under longstanding U.S. sanctions. Without a WHO listing, many countries could not incorporate the vaccines into their national programs, and travelers vaccinated with Cuban shots sometimes found their vaccination status unrecognized abroad.

The timing also worked against them. By the time the Cuban trials published their peer-reviewed results in 2022 and 2023, much of the world had already been vaccinated with other products, and demand for first-generation COVID vaccines was waning. The absence of large international phase 3 trials conducted outside Cuba meant there was less independent corroboration of the efficacy data than existed for vaccines tested across multiple countries and continents. This is not a flaw in the Cuban data per se, but it understandably made some outside observers cautious.

Peer-reviewed publications did eventually appear in well-regarded journals, including The Lancet Regional Health–Americas, Med (a Cell Press journal), and Vaccine, lending the results more credibility in the global scientific community. Still, the practical reality is that Cuba’s vaccines served primarily Cuba and a small number of allied nations, rather than becoming a broadly available tool in the global pandemic response.

The Conjugate Vaccine Concept Beyond COVID

The Soberana line may matter more for what it proved about vaccine design than for the number of arms it reached. Conjugate vaccines have been a staple of bacterial immunization for decades, used against diseases like pneumococcal infection and meningococcal meningitis. Applying the conjugate approach to a viral antigen was genuinely novel. By hitching the SARS-CoV-2 RBD to tetanus toxoid, the Finlay Institute aimed to borrow the robust T-helper cell engagement that conjugate vaccines are known for, something that a simple protein subunit vaccine adjuvanted with aluminum might not achieve as effectively on its own.²

The preclinical and clinical results suggest the strategy works: the conjugate vaccine produced a strong IgG-dominant response, good affinity maturation, and durable B-cell memory. Whether this approach becomes a template for future antiviral conjugate vaccines depends on whether other groups adopt and refine it. Cuba’s researchers have explicitly framed Soberana 02 as a proof of concept that could pave the way for conjugate vaccines against other viruses, and a handful of academic groups elsewhere have taken notice. The platform’s simplicity, thermostability, and the fact that tetanus toxoid is already manufactured at scale worldwide all argue in its favor as a model for rapid-response vaccine development in lower-resource settings.