Could a Second Dose of Novavax be a Game Changer for Adolescent COVID-19 Vaccination?


Heterologous vaccination—or mixing different vaccines—was safe and effective with Novavax and provided enhanced protection against the Omicron variant, a new study found.

Heterologous boosting, or mix-and-match boosting, was found to be more effective than receiving the same COVID-19 shot for both a booster dose and primary vaccine series. In addition to being safe and immunogenic, heterologous boosting was proven to increase neutralizing antibodies more than homogeneous boosting.

However, a new study, published in the Journal of Infection, was the first to evaluate the efficacy of a heterologous second dose in adolescents’ primary vaccine series.1

The Com-COV3 trial was a single-blind, randomized, phase 2, multicenter study that reported the reactogenicity, immunogenicity, and number of COVID-19 infections in adolescents receiving Pfizer-BioNTech (BNT162b2) as a first dose and a second dose of either Pfizer-BioNTech (homologous) or Novavax (NVX-CoV2373; heterologous).

NVX-CoV2373, the recombinant spike (S) protein-based COVID-19 vaccine from Novavax, was recently approved under emergency use authorization for adolescents 12-17 years of age. Previously available only to adults 18 years and older, NVX-CoV2373 offers an alternative to the authorized messenger RNA (mRNA) COVID-19 vaccines.

From September 27, 2021–November 29, 2021, study patients were recruited from 7 United Kingdom National Health Service and academic institutions. Eligible participants included adolescents 12–16 years of age, who had received either no COVID-19 vaccine doses or 1 single dose of Pfizer-BioNTech. All participants were randomized and vaccinated at least 8 weeks after their first dose.

The primary study outcome was solicited systemic reactions for 7 days after the second dose of mixed COVID-19 vaccine schedules. Secondary outcomes evaluated immunogenicity and safety, including solicited local reactions, immunogenicity (anti-spike immunoglobulins [total Ig], cellular responses by ELISpot), safety, cardiac markers, and characterization of anti-nucleocapsid IgG seropositivity.

A total of 148 participants were recruited, averaging 62% female, 14 years of age, and 26% anti-nucleocapsid IgG seropositive pre-second dose. Of them, 132 received a second dose and were randomized 1:1:1 to either 30 µg Pfizer-BioNTech (BNT-30), 10 µg Pfizer-BioNTech (BNT-10), or Novavax.

Participant reactions were largely mild-to-moderate, with lower rates of adverse events in BNT-10 recipients. No vaccine-related serious adverse events occurred.

Compared to BNT-30, at 28 days after receiving a second dose, anti-spike antibody levels were similar for Novavax (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]).

For the Omicron BA.1 and BA.2 variants, neutralizing antibody titers for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for Novavax (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). “Compared to BNT-30, the study authors wrote, “cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose.”

At days 132 and 236 post second dose, cellular responses were similar across all 3 study arms. Follow-up visits continued until August 2022.

Overall, Novavax as a second dose after BNT-30 elicited the highest humoral and peak cellular immune responses. Additionally, the lowest rate of COVID-19 breakthrough infections occurred in patients who received Novavax as their second dose.

“Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic,” concluded the investigators. They noted that the heightened protection of the Novavax heterologous vaccine schedule against Omicron “suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule.”

This article originally appeared on Contagion Live.

1. Kelly E, Greenland M, de Whalley PCS, et al. Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (COM-cov3): A randomised controlled trial. J Infect. Published online 2023. doi:10.1016/j.jinf.2023.06.007
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