Researchers from the United States and The Netherlands have conducted a pre-clinical study supporting the initiation of a Phase 3 trial to test a two-dose regimen of the Janssen Ad26.COV2.S vaccine candidate among adult and elderly individuals.
The team is already testing the vaccine as a single-dose regimen in a Phase 3 trial called ENSEMBLE, following its effectiveness at promoting immune responses among adult and elderly individuals in a Phase 1/2a study.
However, a further dose could potentially improve the magnitude and durability of these immune responses, says the team from Janssen Vaccines and Prevention B.V. in Leiden, the Biomedical Primate Research Centre in Rijswijk, Leiden University Medical Center, and Harvard Medical School in Boston.
Now, the researchers have shown that a second dose of the vaccine administered 8 weeks following an initial dose significantly increased immunogenicity in both adult and aged rhesus macaques, compared with a single immunization.
“These data support the initiation of a two-dose Ad26.COV2.S regimen in a Phase 3 clinical trial in adults and elderly individuals,” writes the team.
The study also showed that the one-dose regimen generated neutralizing antibody responses that lasted at least 14 weeks, thereby supporting the team’s decision to evaluate the single-dose regimen in the current Phase 3 ENSEMBLE trial.
A pre-print version of the paper is available on the bioRxiv* server, while the article undergoes peer review.
Challenges in the race to develop a safe and effective vaccine
Since the COVID-19 pandemic began in Wuhan, China, late last year (2019), researchers have been racing to develop a safe and effective vaccine against the causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
“Ideally, especially in the context of a pandemic, a vaccine provides both an early onset of protection and durable protection,” write Roland Zahn and colleagues.
Although people of all ages are at risk of contracting SARS-CoV-2, the risk of developing severe COVID-19 increases with age, highlighting the importance of ensuring vaccines provide durable immunity among older individuals.
However, among the elderly, the immune response to vaccines tends to be reduced in both magnitude and duration, potentially resulting in reduced vaccine efficacy, say the researchers.
About the Ad26.COV2.S vaccine candidate
The Ad26.COV2.S vaccine candidate encodes a viral surface structure called the SARS-CoV-2 spike protein, which SARS-CoV-2 uses to bind to and infect host cells.
The vaccine induced a prompt and robust immune response after a single-dose among both adult and elderly individuals participating in a Phase 1/2a clinical study.
Based on this data, the protective efficacy of this single-dose regimen is now being tested in the Phase 3 ENSEMBLE trial.
However, “while the advantages of single-dose vaccines, especially for use during a pandemic, are obvious, multiple doses may potentially improve the magnitude and durability of immune responses,” said Zahn and colleagues.
The researchers now plan to initiate a second phase 3 trial – ENSEMBLE 2 – to evaluate the efficacy and durability of a two-dose Ad26.COV2.S regimen among adults and the elderly.
What did the current study involve?
For the current study, the team evaluated the immunogenicity of one- and two-dose Ad26.COV2.S regimens among adult and aged rhesus macaques.
Sixty of the macaques (57 female, 3 male) were aged between 3.3 and 5.0 years (adult group), and 20 of the animals (all female) were aged between 13.75 and 21.9 years (aged group).
SARS-CoV-2 spike-specific antibody responses were tested every two weeks over a period of 14 weeks following the first vaccination using enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay (psVNA).
What were the study outcomes?
Among both adult and aged macaques, SARS-CoV-2 spike-specific binding and neutralizing antibody responses were detected just two weeks following initial vaccination and had significantly increased by week 4 post-immunization.
The kinetics and magnitude of the responses appeared to be similar between adult and aged macaques across all dosing regimens evaluated.
In the case of one-dose regimens, neutralizing antibody responses were maintained for at least 14 weeks post-immunization, providing an early sign of durable immunity elicited by Ad26.COV2.S.
Furthermore, a second dose of the vaccine administered 8 weeks following the initial immunization significantly increased the spike-specific binding and neutralizing antibody responses among both the adult and aged macaques, compared with the single-dose regimen.
The findings support both the current and planned trial
The findings suggest that a two-dose Ad26.COV2.S vaccine regimen may also induce a stronger and more durable immune response in humans, as compared with the one-dose regimen, says the team.
“Overall, these data support our decision to evaluate a single-dose of Ad26.COV2.S in our Phase 3 ENSEMBLE study and also to initiate our second Phase 3 study ENSEMBLE 2, to evaluate the protective efficacy of a two-dose Ad26.COV2.S regimen,” concludes the team.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.