Research Article ISSN 2639-8486

Research Article Clinical Immunology & Research

Subnormal Immunity to Inactivated Poliovirus Vaccine (IPV) in Previously

Vaccinated Human Immunodeficiency Virus (HIV) - Infected Children
Shahana A. Choudhury*

*
Correspondence:
Shahana A. Choudhury, Department of Pediatrics, Meharry
Department of Pediatrics, Meharry Medical College, Nashville, Medical College, 1005 D.B Todd Blvd, Nashville, Tennessee,
Tennessee. Tele: 615-327-6856/ 6332, Fax: 615-327-5835/ 5989

Received: 20 Nov 2022; Accepted: 10 Dec 2022; Published: 30 Dec 2022

Citation: Choudhury SA. Subnormal Immunity to Inactivated Poliovirus Vaccine (IPV) in Previously Vaccinated Human
Immunodeficiency Virus (HIV) - Infected Children. Clin Immunol Res. 2022; 6(1): 1-5.

ABSTRACT
Introduction: Minimal data exists regarding prevalence of immunity to inactivated poliovirus vaccine (IPV) in
previously vaccinated HIV-infected children.

Methods: Antibody titers to IPV against serotypes (ST) 1, 2 and 3 following 3-doses (primary series) and 4th and
5th doses (booster) were examined in 59 children who were born to HIV-infected mothers. Eight of those children
tested negative for HIV by DNA PCR and served as the controls for the 3rd and 4th dose recipients. Anti-polio 1, 2,
3 antibody titers (1/dil) was measured by neutralization assay at Specialty Laboratory in New Jersey. Correlate of
protective immunity (PI) was defined as antibody titer >1:8 for all serotypes. ST specific PI was correlated with
the T cell counts and clinical disease categories within the HIV-infected children. PI status was compared between
the HIV- infected and HIV- uninfected children and between the numbers of vaccine dose recipients within the
HIV-infected children.

Results: Mean age of children at the time of vaccination was 6.6, 18.6 and 66.5 months in the 3rd, 4th and 5th dose
recipients, respectively. The mean age of the HIV-infected and HIV- uninfected children was comparable in the
3-dose group. Among the 3rd and 4th dose recipients, prevalence of PI to all 3 ST was significantly (p= 0.002/ST1,
0.002/ST2 and 0.01/ST3) lower in the HIV-infected, compared to their uninfected counterparts; Within the HIV-
infected children, prevalence of PI to ST 1 and 2 was around 7-10 percent for all dose recipients; and 28 percent
to ST3 for the 5th dose vaccine recipients. The CD4 count was found to be significantly (p=0.009) lower (362/mm3)
in the 5th dose compared to the 3rd dose vaccine recipients (1072 /mm3).

Conclusion: A significantly high proportion of HIV- infected children may remain unprotected against all ST
of IPV even after their booster doses and thus may remain at risk for infection with all 3 ST of poliovirus when
exposed to recipients of the live oral polio vaccine worldwide. Global implementation of IPV over OPV may
be considered to prevent resurgence of poliovirus disease in the growing population of immunocompromised
patients. Extra vigilance in the maintenance of protective immunity to poliovirus serotypes and surveillance of
disease in the immunocompromised host may be deemed necessary for prevention of disease occurrence and
timely diagnosis and treatment.

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Keywords Poliomyelitis is an acute viral disease produced by three
Vaccine, Polio, Antibody, and Protective titer antigenically distinct types of poliovirus (types 1– 3). The primary
mode of transmission of poliovirus is through close association
Introduction with an infected person. Two main routes of person-to-person
Poliovirus disease elimination in the United States is a great success transmission recognized are fecal-oral and droplet spread from
via global polio eradication initiative through mass vaccination and the pharynx. While fecal-oral route is considered more common
improved sanitation strategies. The last outbreak of poliomyelitis means of transmission [10], respiratory droplets is a critical and
due to indigenously acquired wild poliovirus that occurred in the predominant mode of transmission in high income countries with
United States in 1979 was in unvaccinated individuals and United a high proportion of immunocompromised population including
States was certified free of wild poliovirus in September 1994, with human immunodeficiency virus infected individuals. Thus,
similar achievements in the Western Pacific Region in October maintenance of protective immunity to all three serotypes of
2000 and the European Region in June 2002 [1-3]. Elsewhere, in poliovirus is critical to prevent resurgence of this disease in the
parts of Africa and Asia, war continues to serve as a major obstacle immunocompromised population in the United States. The fact
to the eradication initiative [3]. Thus, concerns remain regarding that poliovirus infection is overwhelmingly subclinical and case
reemergence of poliovirus infection with the wild poliovirus fatality rate is as high as 5-10 percent [11] may also pose a threat
not only in Asia and Africa, but also in the United States due to to transmission, morbidity and mortality of this infection in the
threat of imported cases from across the globe and increasing vulnerable immunocompromised population. Therefore, a good
population of immunocompromised hosts including the human level of protective immunity to all three poliovirus serotypes is
immunodeficiency virus -infected individuals. And alterations in deemed necessary to prevent poliovirus infection in HIV-exposed
the social, environmental, biological, and demographic conditions. infected or uninfected children. A recent case of poliovirus disease
with type 3 vaccine derived poliovirus (VDPV) was detected in
The threat of reemergence of the poliovirus disease in the United stool specimens from an infant with primary immunodeficiency
States had always been there due to the increasing number disorder (PID) in China. Surveillance for poliovirus in PID patients
of unvaccinated individuals, immunocompromised hosts and in China has shown an increased detection of immunodeficiency
increasing number of the imported immigrants and refugees from -related (iVDPV) cases [12].
rest of the world where oral polio vaccine is still being used for
routine vaccination purpose. A good example is the recent case of Immune responses to all childhood immunizations are reportedly
poliovirus disease in an unvaccinated person in Rockland County subnormal in HIV-exposed infected or uninfected children
in New York City [4]. compared to those in their immune competent counterparts [13-
19]. Only limited data in the literature is available regarding
The Salk-type or inactivated poliovirus vaccine (IPV) was immunogenicity of the three serotypes of IPV in HIV-exposed
introduced in the United States in 1955 and Sabin-type live infected or uninfected children. A recent South African study
(attenuated) oral poliovirus vaccine (OPV) was introduced in the by Madhi et al. has demonstrated immunogenicity to all three
early 1960s. This broke the chain of wild poliovirus transmission. serotypes of poliovirus one month after IPV vaccination. Following
Cases of vaccine-associated paralytic poliomyelitis (VAPP) the three-dose primary series, the serotypes were lower in infected
continued to occur between 1961-1989; from 1990 through 1999, infants with vertically transmitted HIV when compared with the
61 cases of VAPP were reported [5]. The vaccination policy HIV-exposed uninfected infants [19].
changed from OPV to sequential schedule of IPV followed by
OPV in 1997 and an exclusive IPV schedule was established in Methods
2000. The global polio eradication initiative (GPEI) strategic plan The study was performed as a routine standard of care and data
for 2013-2018 envisioned global withdrawal of OPV vaccine collection during an epidemic of vertically transmitted HIV
by serotype, starting with serotype 2 OPV [6] by mid-2016 (last infection in an academic institution in New York city. The study
natural case occurred in India in 1999). With the onset of HIV was conducted between January 1993 and March 1995. None of
epidemic in the 1990s, exclusive IPV was recommended for the children in the study or control group had received intravenous
infants born to HIV-infected mothers. One of the most frequent immunoglobulin at any time during the study.
sources of immunosuppression in infants from birth to 2 years
of age is exposure to vertical transmission of HIV from infected Study Population
mothers [7]. HIV-exposed but uninfected infants, as well as HIV- Fifty-nine HIV-exposed children born to HIV-infected mothers
exposed and infected infants may be expected to experience lower attending Pediatric Infectious Disease clinic were enrolled into the
immune responses due to indirect immunological consequences study. All infants were tested for HIV infection within one week
of antenatal HIV exposure. Nevertheless, HIV-exposed infants, of birth by HIV deoxyribonucleic acid (DNA) testing (qualitative)
both infected and uninfected, remain at increased risk of under- by polymerase chain reaction (PCR). Infants were followed up to a
immunization and developing vaccine-preventable diseases mean of 6 months of age when repeat blood samples were obtained
including poliomyelitis [8,9]. and retested for HIV DNA by PCR. Of these children, fifty-one
were found infected with HIV and only eight were uninfected.

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HIV-Infected Children Primary vaccination series (3-dose): Mean (± SD) age of the
Related information regarding HIV testing results, antiretroviral ten HIV-infected and six HIV-exposed uninfected infants at
therapy, T cell count and viral load were obtained from the medical vaccination (6.6 [± 0.84] vs.7.7 [± 3.01]) and at serology (12 [±
records of the patients. HIV-infected children were classified 2.90] vs.13.75 [± 3.19]) were comparable. Prevalence of PI to all
clinically as asymptomatic (class N), mildly symptomatic (class serotypes was not significantly different between the two groups.
A), moderately symptomatic (class B) and severely symptomatic
(class C) according to the centers for disease control (CDC) Immunologic Parameters comparing HIV-Infected and
classification system [20]; acquired immunodeficiency syndrome Uninfected Children: Combined 3 and 4-Doses
(AIDS) category was designated if there was a clinical history of Table 1: Comparing Immunologic Parameters; HIV-Exposed Infected
opportunistic infections or CD4 count less than 15 percent for the and Uninfected Children:
age. Combined 3 and 4 -Dose Vaccine Recipients.
HIV Infected HIV Uninfected
n=37 n=8 P
HIV-Exposed Uninfected Children (3-Dose=10 (3-Dose=6 value
Eight infants were HIV-exposed but uninfected who were born to 4-Dose=27) 4-Dose=2)
HIV-infected mothers and seroconverted to uninfected status by Age months at vaccination
6- month of age. These children served as the control group for the mean (± SD) 6.6 (± 0.84) 7.75 (± 3.01) 0.001*
3-dose primary series and 4-dose vaccine recipients. Age months at serology
mean (± SD) 30.27 (± 15.19) 13.75 (± 3.19) 0.004*
Polio vaccination Interval vaccination-serology
All HIV-exposed children (Infected and Uninfected) had received months mean (± SD)
inactivated polio vaccine (IPV). Eighteen (10= infected; 8= 15 (± 11.84) 6 (± 3.70) 0.04*
Immune n (%)
uninfected) children had completed 3-dose primary series of the
Serotype1 3/37 (08 %) 5/8 (62%) 0.002#
IPV. Twenty-nine (27=infected and 2=uninfected) of them had Serotype2 3/37 (08 %) 5/8 (62%) 0.002#
received the 1st booster dose (4 doses) and fourteen HIV-infected Serotype3 3/37 (08 %) 4/8 (50%) 0.01#
children had received the 2nd booster dose (5 doses) of IPV.
*two-tailed t-test #two-tailed Fisher’s exact test.

Determination of antibody titers

Among the 3rd and 4th dose recipients combined (HIV-infected,
Anti-polio 1, 2, 3 antibody titers (1/dil) were measured by
n=37 and HIV-Uninfected, n= 8); prevalence of PI to all 3 ST was
neutralization assay at Specialty laboratories,
significantly (p=0.002/ST1, 0.002/ST2 and 0.01/ST3) lower in
New Jersey (NJ). Correlates of immunities to serotypes 1,2 and 3
the HIV-infected, compared to their uninfected counterparts. The
were defined as antibody titers ≥8 1/dil.
mean (± SD) time-interval between vaccination to serology was 15
Antibody titers were missed to be drawn in two HIV-uninfected
(± 11.84) months for the HIV group and 6 (± 3.70) months for the
children after their 3rd dose in the 4-dose group.
HIV-uninfected control group (p=0.04).
Immunologic and Virologic Studies
Booster doses
T and B cell analyses in the HIV group were performed by flow Table 2: Characteristics of HIV-Infected Children.
cytometry; HIV viral loads and HIV qualitative DNA tests in the 3 Doses 4 Doses 5 Doses
infants were performed at birth, 2-4 and 6 months of age by PCR n=10 n=27 n=14
at Specialty laboratories in NJ. Age months at vaccination
mean (range) 6.6 (6-8) 18.4 (16-30) 66.5 (48-140)
Statistical Analysis Age months at serology
mean (range) 12 (7-15) 37 (19-60) 99.85 (61-168)
No statistical hypotheses were tested, and all evaluations were
Interval vac-serology months
descriptive. Seroprevalence of protective immunities to poliovirus Mean (range) 5.4 (1-9) 18.4 (1-42) 33.2 (2-84)
serotypes 1, 2 and 3 between the HIV and control groups and Protective Immunity n (%)
within the HIV-infected group were compared by two- tailed Serotype1 1/10 (10) 2/27 (07) 1/14 (07)
Fisher’s exact test. Software Intercooled stata version 8.0 was used Serotype2 1/10 (10) 2/27 (07) 1/14 (07)
for statistical analysis. Effects of immunologic (CD4 and B cell Serotype3 1/10 (10) 2/27 (07) 4/14 (28)
count/ mm3) and virologic (viral load) parameters on immunity
CD4/mm3 1072 846 362
status within the HIV group were compared by two- tailed t-test.
mean (10-2530) (4-2840) (0-790)
(range) ns* 0.04* 0.01*
Results p (between (between (between
Fifty-nine HIV-exposed children born to HIV-infected mothers 3 & 4 doses) 4 & 5 doses) 3 & 5 doses)
participated in the study. Of these children, fifty-one were infected CDC class B-C
n (%) 5/10 (50) 10/27 (37) 6/14 (43)
with HIV and only eight were uninfected by HIV DNA PCR. All
*Two-tailed t-test.
participants were born at term.
Immunogenicity
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Within the HIV-infected group, prevalence of PI to all three highest following the first dose of OPV and among immunodeficient
serotypes in the 4-dose recipients were seven percent and in the persons. Since changing to an all-IPV immunization schedule in
5-dose recipients, it was seven percent to serotypes 1 and 2 but 28 2000, there have been only three cases of VAPP reported in the
percent to serotype 3. United States [23-24]. Of these reported cases, two had occurred
in immunocompromised individuals.
Comparing CD4 count by number of doses in the HIV-infected
Children Two phases of acute poliomyelitis have been distinguished: a
nonspecific febrile illness (minor illness) and aseptic meningitis and/
Table 3: Comparing Protective Immunity with Immunologic and Clinical or paralytic disease (major illness) have been recognized in a small
Categories in All HIV-Infected Children (n=51). proportion of patients. The ratio of cases of inapparent infection to
Protective Protective Protective paralytic disease among susceptible individuals ranges from 100:1
immunity immunity immunity
n (%) ST1 n (%) ST2 n (%) ST3
to 1000:1 or more. Progression to maximum paralysis is rapid (2–
No evidence of 4 days); between 2% and 10% of paralytic poliomyelitis cases are
2/17 (12) 1/17 (06) 3/17 (18) fatal. The vaccine polioviruses are able to replicate in the intestinal
suppression of CD4
Evidence of moderate tract of inadequately immunized persons and may be transmitted to
to severe suppression 2/34 (06) 3/34 (09) 4/34 (12) others with inadequate immunity. During these multiple infections,
of CD4
the viruses may regain some of the properties of wild polioviruses,
p 0.59* 1.00* 0.67*
CDC Class N-A
such as transmissibility and neurovirulence. Clinical disease caused
1/21 (05) 0/21 (0) 2/21 (10) by these VDPVs is indistinguishable from that caused by wild
n (%)
CDC Class B-C polioviruses [25]. This raises concern regarding underdiagnosed
3/30 (10) 4/30 (13) 5/30 (16)
n (%) subclinical cases of polio virus disease in the immunocompromised
p 0.63* 0.13* 0.68* and unvaccinated population which may remain unrecognized. Thus,
*two-tailed Fisher’s exact test. the actual number of poliovirus disease in the United States may be
underestimated. Because inapparent infection with OPV or wild virus
CD4 count/mm3 was significantly (p=0.04) lower in the 5-dose strains no longer contributes to the establishment or maintenance of
(362/mm3) compared to the 4-dose (846/mm3) vaccine recipients poliovirus immunity in the United States, universal vaccination of
and significantly (P=0.01) lower in the 3-dose (1072/mm3) infants and children is the only means of establishing and maintaining
compared to the 5-dose recipients (362/mm3). population immunity against poliovirus to prevent poliomyelitis
cases and epidemics caused by importation of wild virus into the
Comparing immune responses between 4 and 5 dose recipients United States. Although seroprevalence studies have demonstrated
in the HIV-infected Children: No high level of immunity in children [26], outbreaks of poliomyelitis
Difference was noted for serotypes 1, 2 and 3. continue to be reported among religious groups in the United States
[27,28]. This finding reiterates the importance of developing further
Discussion strategies to detect and prevent subclinical or clinical poliovirus
This study provides important immunogenicity data following disease in the immunocompromised population. Such strategies may
the administration of IPV in HIV-exposed infected and HIV- include 1) surveillance and monitoring of protective immunities
exposed uninfected infants and children in the United States. to poliovirus serotypes during febrile illnesses, or even as routine
There is paucity of data evaluating immunogenicity of IPV in this standard of care in this population. The poliomyelitis surveillance
special group of immunocompromised patients. Although study system is already in place to detect importation of wild poliovirus
was performed about two decades ago; the data is still relevant into the United States and detect the presence of vaccine-derived
given the fact there is not enough data of polio immunogenicity poliovirus in the United States. 2) Importance of rapid identification
in this group of immunocompromised people and this data can be of suspected poliomyelitis cases is critical for identifying possible
extrapolated to other growing population of immunocompromised wild poliovirus transmission. Rapid detection of wild or virus-related
hosts in the United States. Although infants and children born cases permits the timely implementation of controls to limit the spread
to HIV-infected mothers currently are not getting infected due of imported wild poliovirus or cVDPVs and maintain the eradication
to implementation of highly active antiretroviral therapy in the of wild poliovirus in the United States. Moreover, rapid investigation
pregnant women, concerns remain regarding circulating live polio of suspected cases will allow collection of specimens for poliovirus
virus from OPV recipients and susceptibility of the vulnerable isolation, which is critical for confirming whether a case of paralytic
populations globally. The recent case of VAPP in Rockland poliomyelitis is the result of wild or vaccine-related virus infection.
county in New York city underscores the importance of these data A rapid antigen-based test or polymerase chain reaction- based test
when extrapolated to the immunocompromised and unvaccinated may need to be developed. 3) Disease Reduction Goals: There have
population even in the United States. been only three cases of VAPP reported in the United States since
2000, when the use of OPV was discontinued. High coverage with
All reported cases of paralytic poliomyelitis in the United States poliovirus vaccine is required to maintain elimination of poliomyelitis
have been vaccine-associated VAPP [20-22]. The risk of VAPP is in the United States until global eradication is achieved.

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