Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in nonhuman primates is coincident with an anamnestic antibody response in the lower airway

Abstract

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody binding titers also decreased in bronchoalveolar lavage (BAL). Four days after challenge, virus was unculturable in BAL and subgenomic RNA declined ~3-log10 compared to control animals. In nasal swabs, sgRNA declined 1-log10 and virus remained culturable. Anamnestic antibody responses (590-fold increase) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.

Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

“…When compared with boosting with the historical mRNA-1273 vaccine, which increased neutralizing antibody responses against BA.1 and BA.2 to a lesser degree, the differences in virological protection in the upper and lower airways were modest. When mice were given a high-dose mRNA-1273 primary vaccination series, there was no benefit of the BA.1-matched booster compared with the mRNA-1273 booster, which agrees with recent data from nonhuman primates (Gagne et al, 2021). However, when mice were given a low-dose primary vaccination series, protection against lung infection and inflammation was slightly greater in animals boosted with the BA.1-matched mRNA-1273.529 vaccine.…”

Reappraising the Value of HIV-1 Vaccine Correlates of Protection Analyses

“…The successful evaluation of neutralizing MAbs in human trials, NHP experiments, and small-animal models reinforces that virus neutralization is sufficient for protection against COVID-19 ( 63 , 129 , 130 , 133 , 134 , 137 , 138 ). When virus challenges of NHPs are delayed for a long period (up to 1 year) after vaccination, however, the initially high and protective serum NAb titers had decayed markedly (∼7-fold against a D614G mutant from week 6 to week 48 [ 139 ]). Upon challenge, the animals became infected, as judged by virus replication in the upper respiratory tract, but did not develop pulmonary symptoms.…”

“…Upon challenge, the animals became infected, as judged by virus replication in the upper respiratory tract, but did not develop pulmonary symptoms. The explanation may be that anamnestic immune responses, activated over a few days, curbed virus replication ( 139 ). Similar mechanisms may be in play in humans after their initial NAb responses have waned but when immune memory has been established.…”

Durable immunogenicity, adaptation to emerging variants, and low-dose efficacy of an AAV-based COVID-19 vaccine platform in macaques

“…[1][2][3][4] As vaccination campaigns advanced, the risk of serious disease and death in the vaccinated was greatly reduced; 5 however, vaccine effectiveness declined due to waning immunity, particularly of mRNA-based vaccines. [6][7][8] The emergence of novel variants further exacerbates the risk for breakthrough infection. Lastly, studies suggest that, when vaccinated, transmission remains significant.…”

“…29,30 Compounding the threat of immune-escape SARS-CoV-2 variants, the immunity elicited by natural infection or by mRNA vaccines appears to wane within months after immunization. Indeed, antibody titers induced by mRNA-based vaccines progressively wane after two doses of immunization by as much as 10-fold in 6 months, [6][7][8] requiring a booster to recover protective immunity. Other vaccines, such as the single-shot Ad26, appear to perhaps provide more durable immunity, but overall demonstrate lower protection from disease and reduced antibody levels compared with mRNA at its peak efficacy.…”