Factors Associated with Neutralizing Antibody Responses following 2-Dose and 3rd Booster Monovalent COVID-19 Vaccination in Japanese People Living with HIV

Abstract

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4⁺ count, CD4⁺/CD8⁺ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4⁺ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH.

Keywords: COVID-19 vaccination; HIV; SARS-CoV-2; neutralizing antibodies; variants of concern.

Figure 1

Neutralizing antibody (NAb) titers following 2-dose vaccination. (A) Distribution of NAb titers against Wuhan (expressed as reciprocal IC₅₀) of all the study participants (n = 82). The red line denotes the median NAb titers while the dotted line represents the limit of detection (300 µg/mL (reciprocal = 0.003)). (B) Comparison of NAb titers between recipients of BNT162b2 (Pfizer) and mRNA-1273 (Moderna) by Mann–Whitney ranked U test.

Figure 2

Changes in neutralizing antibody (NAb) titers against Wuhan and variants of concern (VOCs) following 3rd booster vaccination. (A) Changes in NAb titers against Wuhan and VOCs (Delta, Omicron BA.1, and Omicron BA.2) following 2-dose and 3rd booster vaccination in a subset of 3rd booster vaccinated participants (n = 18). Changes in the NAb titers of previously identified low-NAb-titer participants (n = 5) are highlighted in red. The p-values were computed by Wilcoxon ranked test. Median fold changes in NAb titers, alongside p-values, are indicated within each panel. (B) Spearman correlation between age and NAb titers against Wuhan, and VOCs following 3rd booster vaccination. The line of best fit (red line) was generated by linear regression.

Figure 3

Age subgroup differences in factors associating with neutralizing antibody (NAb) titers following 2-dose vaccination. Spearman correlation between (A) age, (B) CD4⁺ count, (C) CD4⁺/CD8⁺ ratio, and (D) hsCRP levels and IgG NAb titers against Wuhan in younger (≤48 years) and older (>48 years) participants. hsCRP; high sensitivity C-reactive protein. Lines of best fit (black and red) were generated by linear regression.