PROTECTION AGAINST HETEROLOGOUS CHALLENGE 1 YEAR AFTER INFANT SARS-CoV-2 IMMUNIZATION
Topics in Antiviral Medicine
; 31(2):336, 2023.
Article
in English
| EMBASE | ID: covidwho-2317251
ABSTRACT
Background:
Although mRNA SARS-CoV-2 vaccines have received emergencyuse- authorization for infants age 6 months and older, vaccine uptake is slow, stressing that questions of safety and durability of vaccine efficacy remain prominent. Method(s) Infant rhesus macaques (RMs) (n=8/group) at 2 months of age, comparable to human toddler age, were immunized intramuscularly at weeks 0 and 4 with 30mug stabilized prefusion SARS-CoV-2 S-2P spike (S) protein (Washington strain) encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or 15mug S protein mixed with 3M-052 in stable emulsion (Protein). At 1 year, vaccinated and age-matched unvaccinated RM (n=8) were challenged intranasally (106pfu) and intratracheally (2x106pfu) with B.1.617.2. Lung radiographs and pathology were blindly assessed, viral N gene RNA (vRNA) copies were measured by qPCR in pharyngeal swabs and lung, and neutralizing antibody and peripheral blood T cell responses were measured. Result(s) At 1 year, D614G-specific neutralizing antibody (nAb) titers were still detectable in the Protein (ID50=755;range 359-1,949) and mRNA-LNP groups (ID50=73;range 41-240). Both vaccines also induced cross-neutralizing antibodies to B.1.617.2. Peripheral blood CD4+ T cell responses to the ancestral spike protein at week 52 did not differ between the groups. However, median CD8+ T cell responses were higher (p=0.002, Mann Whitney) in the mRNA-LNP group (2.8%;range 0.9%-7.1%) compared to the Protein group (0.8%;range 0.1%-1.6%). Control RMs had significantly higher median vRNA copies/ml (1.4+/-2.7x108) in day 4 pharyngeal swabs compared to Protein (3.8+/-6.8x103) or mRNA-LNP (4.4+/-9.7x105) vaccinated RMs. Severe lung pathology was observed in 7 of 8 controls compared to 1 of 8 or 0 of 8 RMs in the mRNA-LNP or Protein group respectively. Protection against lung inflammation was associated with nAb titers (r=-0.592, p=0.003) (Figure 1). Conclusion(s) These results demonstrate that despite lower vaccine doses compared to adults, both protein and mRNA vaccines were safe, induced durable immune responses and provided comparable protective efficacy against infection with a heterologous SARS-CoV-2 variant in infants, implying that early life vaccination of human infants may lead to durable immunity. Neutralizing ID50 antibody titers are a correlate of protection in infant RMs challenged with SARS-CoV-2.
adult; animal experiment; animal model; antibody titer; CD4+ T lymphocyte; CD8+ T lymphocyte; conference abstract; controlled study; drug therapy; drug toxicity; emulsion; female; human; id50; immune response; immunization; low drug dose; lung disease; male; nonhuman; pneumonia; rhesus monkey; SARS-CoV-2 Delta; Severe acute respiratory syndrome coronavirus 2; spike; T lymphocyte; throat swab; toddler; vaccination; Washington; X ray film; broadly neutralizing antibody; endogenous compound; lipid nanoparticle; messenger RNA; RNA vaccine; telratolimod; virus spike protein
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2023
Document Type:
Article
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