Novavax as a Second Dose: A Potential Game Changer for Adolescent COVID-19 Vaccination

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.

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.”