mRNA intramuscular vaccination produces a robust IgG antibody response in advanced neuromuscular disease

Abstract

SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Here, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use.

Keywords: COVID-19; Dried blood spots; ELISA; IgG; Muscular dystrophy; Neuromuscular; Receptor binding domain; SARS-CoV-2; Serological testing.

Fig. 1

Anti-receptor binding domain (RBD) IgG and percent surrogate neutralization after natural infection and vaccination. (A) Median anti-RBD IgG levels collected from neuromuscular (NMD) participants (22.9 µg/ml; n = 14) was significantly higher than individuals who were unvaccinated but had outpatient COVID-19 infection (COVID-19+) (2.1 µg/ml; n = 88), and not statistically different from community acquired vaccinated controls (vax) (43.3 µg/ml; n = 59). Kruskal-Wallis test was used to evaluate statistical significance. * P < 0.001. (B) Using an in vitro surrogate neutralization assay, median percent surrogate neutralization of Wuhan spike-ACE2 receptor binding was increased in vaccinated NMD participants (95.3%; n = 13) compared to community COVID-19+ samples (42.4%; n = 50), and not statistically different than vaccinated controls (98.2%; n = 14). Kruskal-Wallis tests were used to evaluate statistical significance. * P < 0.001. NMD patients on glucocorticoid steroids are indicated in maroon color.