SARS-CoV-2 Omicron Variant Neutralization after Third Dose Vaccination in PLWH

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• mRNA vaccines elicit neutralizing antibodies against SARS-CoV-2 strains.
• The Omicron (BA.1) variant exhibits immune escape properties.
• People living with HIV (PLWH) may have altered immune responses to vaccination.

Purpose of the Study:

• To measure neutralizing antibody titers against SARS-CoV-2 Omicron (BA.1) and Wuhan-D614G (W-D614G) in vaccinated PLWH and healthcare workers (HCW).
• To compare antibody responses before and after a third mRNA vaccine dose.
• To assess the impact of CD4 nadir and current CD4 count on neutralization capacity in PLWH.

Main Methods:

• Serum samples from 106 PLWH and 28 HCW were collected before and after a third mRNA vaccine dose.
• Neutralizing antibody titers (nAbsT) against Omicron (BA.1) and W-D614G strains were measured.
• Statistical analyses compared nAbsT levels between groups and across variants, considering CD4 counts.

Main Results:

• Before the third dose, undetectable nAbsT against BA.1 were prevalent (88% in PLWH low CD4 nadir, 80% in PLWH high nadir, 100% in HCW).
• After the third dose, detectable nAbsT against BA.1 increased significantly (89% in PLWH low nadir, 100% in PLWH high nadir, 96% in HCW).
• Post-vaccination nAbsT against BA.1 were lower than against W-D614G in HCW and PLWH with high CD4 nadir. In PLWH with low CD4 nadir, current CD4 count influenced neutralization breadth.

Conclusions:

• A third mRNA vaccine dose enhances neutralizing antibody responses against SARS-CoV-2 Omicron (BA.1) in vaccinated PLWH and HCW.
• Neutralization capacity against Omicron (BA.1) remains lower compared to the ancestral W-D614G strain post-vaccination.
• Current CD4 count may play a role in the breadth of SARS-CoV-2 neutralization in PLWH with a low CD4 nadir.