1. Both the Johnson & Johnson-Janssen (JJJ) and mRNA boosters provided an acceptable safety profile and immunogenic response in healthcare workers who received a primary JJJ vaccine.

2. After receiving a primary JJJ vaccine, patients had the strongest immunogenic response after receiving an mRNA booster.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The JJJ vaccine has been demonstrated to induce lower levels of Covid-19 spike protein-specific antibodies than the mRNA-based vaccines. Therefore, it has been proposed that mixing and matching Covid-19 vaccines enhances both the flexibility of vaccine administration and may induce broader immune responses. However, there is a gap in knowledge as to understanding the immunologic and safety assessments of the effect of mRNA boosters in persons who received a priming JJJ dose. This study found that boosting with mRNA vaccines provided the most efficient response in patients who received the single-shot JJJ dose as their primary vaccine. This study was limited by factors such as evaluating boosters in healthcare workers who are generally younger than participants in other studies of homologous vaccine regimens and their participants did not have severe coexisting conditions. Nevertheless, these study’s findings are significant, as they demonstrate that both homologous and heterologous booster regimens for those who received the JJJ primary dose provide an immunogenic response and increase vaccine effectiveness against infection and transmission of Covid-19.

Click to read the study in NEJM

Relevant Reading: Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina

In-Depth [randomized controlled trial]: This single-blind multicenter, randomized controlled trial involved healthcare workers who received a JJJ vaccine as their primary vaccination regimen. Patients were assigned to receive no booster, a Pfizer-BioNTech booster, a Moderna booster, or a JJJ booster. Healthcare workers who were between 18 and 75 years of age and did not have severe coexisting factors or conditions were eligible for the study. Patients who had receipt of treatment for cancer, use of immunosuppressant agents, solid-organ or bone marrow transplant, or a history of Covid-19 infection were excluded from the study. The primary outcome was the level of S-specific binding antibodies. Outcomes in the primary analysis were conducted via Mann-Whitney U tests to assess differences in log-transformed titer values. Based on the analysis, homologous or heterologous booster vaccination resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses compared to only receiving a single JJJ vaccine dose. Additionally, heterologous boosters had a significantly larger increase in binding antibodies than with the homologous JJJ booster. The Moderna booster was also found to be the most immunogenic and associated with higher reactogenicity than the Pfizer-BioNTech and JJJ vaccines. Overall, this study demonstrated that vaccine boosters after receiving the single dose JJJ vaccine, whether homologous or heterologous, confer immunogenicity and improve vaccine effectiveness against infection and transmission of Covid-19. This can further help guide global discussions on the use of boosters, the prime-boost interval target population, and the level of Covid-19 circulation.

Image: PD

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