1. Homologous and heterologous booster vaccines had an acceptable safety profile in adults who completed a primary Covid-19 vaccine regimen.

2. Homologous and heterologous booster vaccines were immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) have been utilized in the United States to provide high levels of protection against severe illness and death of the delta and omicron waves. However, there is a gap in knowledge as to understanding whether heterologous boosters offer immunologic advantages to extend the breadth and longevity of protection, as the option to use heterologous boosters could simplify the logistics of administering such vaccines if the primary series received was irrelevant to deciding booster choice. This study found that boosting with any of the 3 vaccines authorized for use in the US provides an anamnestic response in persons who had previously received a primary series of any of these vaccines, and homologous and heterologous boosters provided similar levels of immunogenic response. This study was limited by factors such as a small sample size that is insufficient for comparing among groups, as well as an insufficient interim follow-up period that could not identify rare or late adverse effects. Nevertheless, these study’s findings are significant, as they demonstrate that both homologous and heterologous boosters offer similar levels of protection and will provide a similar immune response against Covid-19 regardless of the primary vaccine regimen received.

Click to read the study in NEJM

Relevant Reading: Effects of a Prolonged Booster Interval on Neutralization of Omicron Variant

In-Depth [open-label clinical trial]: This open-label clinical trial was conducted at 10 sites in the United States, following 458 participants. 154 received the Moderna booster, 150 received the Johnson & Johnson-Janssen booster, and 153 received the Pfizer-BioNTech booster. Patients who were between 18 to 55 years and received the designated booster vaccine after receiving informed consent were eligible for the study. Patients who were pregnant or who were unable to give informed consent were excluded from the study. The primary outcome was safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. Outcomes in the primary analysis were conducted via descriptive analysis and unadjusted point estimates. Based on the analysis, reactogenicity was similar to that reported for the primary vaccine series. For all combinations of booster and primary vaccine regimen, antibody neutralizing titers increased by a factor of 4 to 73 and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers from 4 to 20 while heterologous boosters increased titers by a factor of 6 to 73. No safety concerns were identified across any of the vaccine combinations. Overall, this study demonstrated that both homologous and heterologous vaccines provide an immune response against Covid-19 with similar adverse events and reactogenicity regardless of the primary vaccine regimen.

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