Understanding the humoral immune response induced by the inactivated COVID-19 vaccine and the impact of CD4 cell count on vaccine response in PLWH were essential in decision-making regarding future disease control and revaccination strategies. It is important to ensure adequate protection against infection in the vulnerable population, especially to prevent the emerging new variants. This cross-sectional study extends the existing literatures [8–16] by providing more comprehensive evidence to assess the inactivated COVID-19 vaccine response among PLWH.
We found that PLWH and HNC had a similar humoral immune response to the inactivated COVID-19 vaccine at the 3rd month after two doses of inactivated COVID-19 vaccination. Even though nAbs titers and seroconversion rate of nAbs in PLWH were both lower than that in the HNC, after adjusting for potential confounders, the differences disappeared. These findings are consistent with the results of other studies conducted in South Africa and UK, which suggested that the immune responses produced by the adenovirus vector-based COVID-19 vaccine among PLWH are similar to those among HNC [12, 13]. Other studies about the immune response to mRNA COVID-19 vaccine among PLWH also reported similar humoral immune response to the healthy controls [8]. The results indicate that PLWH should complete both doses of inactivated COVID-19 vaccine to achieve good protection. Studies have shown that two doses of inactivated CoronaVac vaccines offer high levels of protection against severe disease and death among all age group[21].
Several studies have shown that PLWH have lower responses to some types of vaccine, including hepatitis A, hepatitis B, and influenza vaccine. These responses are dependent on the level of CD4 cell count [22–25]. CD4 cell is pivotal in orchestrating both the humoral and cellular immune responses to vaccination and has an essential impact on antibody production [26]. Some studies also suggested that PLWH with low CD4 cell count had a poor response to the COVID-19 vaccine while PLWH with CD4 cell count in a healthy range mounted equivalent vaccine responses to those in HIV-negative people [27, 28]. Our study found a statistically lower titer and seroconversion rate of nAbs among PLWH with the CD4 cell count<200 µL (versus the group CD4 ≥ 500/µL). We also found a positive correlation between CD4 cell count and nAbs titers in PLWH and CD4 cell count<200/µL independently predicted lower nAbs titers. The results indicate that PLWH, especially those with CD4 cell count<200/µL were still relatively vulnerable even after two doses of inactivated COVID-19 vaccination. A study on the infection forms of SARS-CoV-2 infection among PLWH showed that PLWH were more likely to be an asymptomatic carrier[29]. Prolonged SARS-CoV-2 infection in advanced PLWH with profound immunosuppression or without ART would drive SARS-CoV-2 virus evolution[30], which may be the reason that 'omicron' emerged. We should expand COVID-19 vaccination coverage and promote the uptake among the lower- and middle-income countries where the COVID-19 vaccination rates are still low[31], and especially among PLWH. Furthermore, we should strengthen the aggressive ART for PLWH, especially for those with low CD4 cell count, to increase the CD4 cell count and strengthen their immune response level to vaccines and achieve longer duration of vaccines. This is not just to prevent PLWH from SARS-CoV-2 infection but to prevent the emergence of new variants.
This study has several limitations. First, the sample size of HNC was relatively small. Studies with larger sample size will be more conductive to identify individuals who are particularly vulnerable to the impact of SARS-CoV-2 infection and develop targeted vaccination interventions. Second, imbalance existed in the sex distribution of PLWH, which may lead to some bias in our results. However, a previous study found the responses to inactivated COVID-19 vaccination had no significant differences between male and female, which may mitigate some of the sex imbalance in this study [32]. Third, the T-cell responses against the inactivated COVID-19 vaccines weren’t investigated in our study. Long-term follow-up for PLWH with inactivated COVID-19 vaccination will be performed in our further study, and the durability and quality of humoral and cellular responses of inactivated COVID-19 vaccines will be evaluated.
In conclusion, our study indicated that PLWH with lower CD4 cell count showed a weaker humoral immune response to inactivated COVID-19 vaccination, especially those with CD4 cell count<200 /µL. Additional measures against COVID-19 are needed for PLWH who have low CD4 cell count.